Acquired Immunodeficiency SyndromePhase 1ENCORE3NCT00985543
Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.
A Phase 1 study testing lopinavir/ritonavir in people with Acquired Immunodeficiency Syndrome, run by Kirby Institute at 1 site in United Kingdom.
Trial summary
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV-negative healthy volunteers of: 1. Lopinavir/ritonavir 400/100 mg twice daily 2. Lopinavir/ritonavir 200/150 mg twice daily 3. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Acquired Immunodeficiency Syndrome
- What is being tested?
- lopinavir/ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2009to Jan 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month after the study
Who cannot join
- Any significant acute or chronic medical illness
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B core and/or C antibodies and/or hepatitis B surface antigen
- Positive blood screen for HIV-1 and/or 2 antibodies
- Current or recent (within 3 months) gastrointestinal disease
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
Show all 11Show fewer
- Exposure to any investigational drug or placebo within 3 months of first dose of study drug
- Consumption of grapefruit, or Seville oranges or any grapefruit or Seville orange containing product within one week of first dose of study drug and for the duration of the study
- Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
- Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
- Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
St Stephen's Centre, Chelsea and Westminster Hospital
London, SW10 9TH
About this study
Official title: Pharmacokinetics of Plasma Lopinavir/Ritonavir Over a 12 Hour Dosing Interval Following Administration of 400/100, 200/150, and 200/50 mg Twice Daily to HIV-negative Healthy Volunteers
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV-negative healthy volunteers of:
- Lopinavir/ritonavir 400/100 mg twice daily
- Lopinavir/ritonavir 200/150 mg twice daily
- Lopinavir/ritonavir 200/50 mg twice daily
Read the detailed description
Data during the development of lopinavir/ritonavir showed that lower drug doses had similar efficacy to the standard dose of 400/100mg twice daily. Lower drug doses are also associated with limited toxicity and cost.
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir following administration to male and female HIV-negative volunteers of 400/100mg, 200/150mg and 200/50mg lopinavir/ritonavir twice daily. Each dosing phase will last for 7 days and each phase will be separated by a 7-day wash-out period. Pharmacokinetic evaluations will be made over a 12-hour interval at the end of each dosing phase.
Healthy subjects as determined by their medical history and physical examinations will be eligible to participate in the study. HIV-positive subjects will not be recruited as there is a risk that HIV-resistant mutations will be selected by an experimentally reduced dose of lopinavir/ritonavir. There is no reason to presume that there is any meaningful difference in the metabolic processing of lopinavir/ritonavir between HIV-infected and HIV-uninfected people.
- Conditions
- Acquired Immunodeficiency Syndrome
- Being tested
- lopinavir/ritonavir
- Keywords
- HIV, ART, HAART, Pharmacokinetics, Lopinavir/ritonavir, Lower dose selection
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lopinavir/ritonavirDrug
Also called Meltrex, Ritonavir
Each participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.
| Study group | Role | What they receive |
|---|---|---|
| LPV/r 400/100 mg | Active comparator | Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID)) Receives: Drug: lopinavir/ritonavir |
| LPV/r 200/150 mg | Experimental | Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID) Receives: Drug: lopinavir/ritonavir |
| LPV/r 200/50 mg | Experimental | Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID) Receives: Drug: lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.
Measured: at the end of each 7-day dosing phase
Secondary outcomes (1)
Adverse Events
Number of reported adverse events, severity of adverse events and relationship to study drug was assessed by questions, physical examination and laboratory parameters. Adverse event data was used to assess the safety and tolerability of low lopinavir/ritonavir doses.
Measured: Up to 11 weeks from screening to final study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Investigators
- Marta Boffito, MD PhD, Principal investigator, Chelsea and Westminster Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00985543
- Sponsor's protocol ID
- NCHECR-ENCORE3
- Acronym
- ENCORE3
- Status last verified
- Mar 2011
- First submitted
- 25 Sep 2009
- Last updated
- 29 Mar 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jackson A, Hill A, Puls R, Else L, Amin J, Back D, Lin E, Khoo S, Emery S, Morley R, Gazzard B, Boffito M. Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers. J Antimicrob Chemother. 2011 Mar;66(3):635-40. doi: 10.1093/jac/dkq468. Epub 2010 Dec 17.
PubMed 21172791
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Plasma Lopinavir/Ritonavir Over a 12 Hour Dosing Interval Following Administration of 400/100, 200/150, and 200/50 mg Twice Daily to HIV-negative Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00985543
- Acronym / sponsor ID
- ENCORE3 / NCHECR-ENCORE3
- Conditions
- Acquired Immunodeficiency Syndrome
- Keywords
- HIV, ART, HAART, Pharmacokinetics, Lopinavir/ritonavir, Lower dose selection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Study start
- Oct 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 28 Sep 2009 (estimated)
- Results
- Posted 29 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV-negative healthy volunteers of:
- Lopinavir/ritonavir 400/100 mg twice daily
- Lopinavir/ritonavir 200/150 mg twice daily
- Lopinavir/ritonavir 200/50 mg twice daily
Detailed description
Data during the development of lopinavir/ritonavir showed that lower drug doses had similar efficacy to the standard dose of 400/100mg twice daily. Lower drug doses are also associated with limited toxicity and cost.
The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir following administration to male and female HIV-negative volunteers of 400/100mg, 200/150mg and 200/50mg lopinavir/ritonavir twice daily. Each dosing phase will last for 7 days and each phase will be separated by a 7-day wash-out period. Pharmacokinetic evaluations will be made over a 12-hour interval at the end of each dosing phase.
Healthy subjects as determined by their medical history and physical examinations will be eligible to participate in the study. HIV-positive subjects will not be recruited as there is a risk that HIV-resistant mutations will be selected by an experimentally reduced dose of lopinavir/ritonavir. There is no reason to presume that there is any meaningful difference in the metabolic processing of lopinavir/ritonavir between HIV-infected and HIV-uninfected people.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LPV/r 400/100 mg | Active comparator | Drug: lopinavir/ritonavirLopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID)) |
| LPV/r 200/150 mg | Experimental | Drug: lopinavir/ritonavirLopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID) |
| LPV/r 200/50 mg | Experimental | Drug: lopinavir/ritonavirLopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
Key exclusion criteria (11 listed)
- Any significant acute or chronic medical illness
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B core and/or C antibodies and/or hepatitis B surface antigen
- Positive blood screen for HIV-1 and/or 2 antibodies
- Current or recent (within 3 months) gastrointestinal disease
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 |
|---|---|---|
| lopinavir/ritonavirAlso: Meltrex, RitonavirEach participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period. | Drug | LPV/r 200/150 mg, LPV/r 200/50 mg, LPV/r 400/100 mg |
Primary outcome
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
Time frame: at the end of each 7-day dosing phase
Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.
1 secondary outcome
Adverse Events
Time frame: Up to 11 weeks from screening to final study visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21172791Jackson A, Hill A, Puls R, Else L, Amin J, Back D, Lin E, Khoo S, Emery S, Morley R, Gazzard B, Boffito M. Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers. J Antimicrob Chemother. 2011 Mar;66(3):635-40. doi: 10.1093/jac/dkq468. Epub 2010 Dec 17.
Related trials for Acquired Immunodeficiency Syndrome
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Marta Boffito, MD PhD principal investigator
Chelsea and Westminster Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing lopinavir/ritonavir in people with Acquired Immunodeficiency Syndrome, run by Kirby Institute at 1 site in United Kingdom.
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 6 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 29 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h). (time frame: at the end of each 7-day dosing phase). 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 NCT00985543, 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 29 Mar 2011.