Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

Acquired Immunodeficiency Syndrome Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00985543
• Other study ID #: NCHECR-ENCORE3
• Status: Completed
• Phase: Phase 1
• First received: September 25, 2009
• Last updated: March 2, 2011
• Start date: October 2009
• Est. completion date: January 2010

Study information

• Verified date: March 2011
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical 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. Lopinavir/ritonavir 200/50 mg twice daily

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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:

1. Any significant acute or chronic medical illness

2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations

3. Positive blood screen for hepatitis B core and/or C antibodies and/or hepatitis B surface antigen

4. Positive blood screen for HIV-1 and/or 2 antibodies

5. Current or recent (within 3 months) gastrointestinal disease

6. 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

7. Exposure to any investigational drug or placebo within 3 months of first dose of study drug

8. 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

9. 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.

10. 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

11. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• lopinavir/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.

Locations

Country	Name	City	State
United Kingdom	St Stephen's Centre, Chelsea and Westminster Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	at the end of each 7-day dosing phase	No
Secondary	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.	Up to 11 weeks from screening to final study visit	Yes