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Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses. (ENCORE3)

Primary Purpose

Acquired Immunodeficiency Syndrome

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

lopinavir/ritonavir

About this trial

This is an interventional treatment trial for Acquired Immunodeficiency Syndrome focused on measuring HIV, ART, HAART, Pharmacokinetics, Lopinavir/ritonavir, Lower dose selection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
1. 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
2. Male or non-pregnant, non-lactating females
3. Between 18 to 65 years, inclusive
4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
5. 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

Exclusion Criteria:

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
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

Sites / Locations

St Stephen's Centre, Chelsea and Westminster Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

LPV/r 400/100 mg

LPV/r 200/150 mg

LPV/r 200/50 mg

Arm Description

Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))

Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)

Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00985543

First Posted

September 25, 2009

Last Updated

March 2, 2011

Sponsor

Kirby Institute

1. Study Identification

Unique Protocol Identification Number

NCT00985543

Brief Title

Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

Acronym

ENCORE3

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2011

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Kirby Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acquired Immunodeficiency Syndrome

Keywords

HIV, ART, HAART, Pharmacokinetics, Lopinavir/ritonavir, Lower dose selection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LPV/r 400/100 mg

Arm Type

Active Comparator

Arm Description

Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))

Arm Title

LPV/r 200/150 mg

Arm Type

Experimental

Arm Description

Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)

Arm Title

LPV/r 200/50 mg

Arm Type

Experimental

Arm Description

Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)

Intervention Type

Drug

Intervention Name(s)

lopinavir/ritonavir

Other Intervention Name(s)

Meltrex, Ritonavir

Intervention Description

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.

Primary Outcome Measure Information:

Title

Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).

Description

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.

Time Frame

at the end of each 7-day dosing phase

Secondary Outcome Measure Information:

Title

Adverse Events

Description

Time Frame

Up to 11 weeks from screening to final study visit

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marta Boffito, MD PhD

Organizational Affiliation

Chelsea and Westminster Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St Stephen's Centre, Chelsea and Westminster Hospital

City

London

ZIP/Postal Code

SW10 9TH

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

21172791

Citation

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.

Results Reference

derived

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Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

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