Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

Phase 1

Completed

Conditions: Acquired Immunodeficiency Syndrome

Interventions: Drug: lopinavir/ritonavir

Registration Number: NCT00985543

Lead Sponsor: Kirby Institute

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:

1. Lopinavir/ritonavir 400/100 mg twice daily

2. Lopinavir/ritonavir 200/150 mg twice daily

3. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LPV/r 200/50 mg	lopinavir/ritonavir	Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)
LPV/r 400/100 mg	lopinavir/ritonavir	Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))
LPV/r 200/150 mg	lopinavir/ritonavir	Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse Events	Up to 11 weeks from screening to final study visit	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.