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Pharmacokinetics of Lamivudine at Two Different Doses (ENCORE2)

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Lamivudine (3TC)

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, HAART, ART, Pharmacokinetic, Healthy volunteers, 3TC, Lamivudine

Eligibility Criteria

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

Inclusion Criteria:

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 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
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 Type

Active Comparator

Arm Label

3TC 300mg/150mg

3TC 150mg/300mg

Arm Description

Group 1: Participants will be administered 3TC 300 mg once daily orally for 10 days. A 10 day wash-out period will follow (days 11-20). From day 21, participants will be administered 3TC 150 mg once daily for 10 days

Group 2: Participants will be administered 3TC 150 mg once daily orally for 10 days. A 10 day wash-out period will follow (days 11-20). From day 21, participants will be administered 3TC 300 mg once daily for 10 days

Outcomes

Primary Outcome Measures

Plasma concentrations of 3TC and intracellular concentrations of its active anabolite 3TC-TP as measured by the Area Under the Curve (AUC 0-24h).

Concentrations will be compared after the administration of 3TC 300 mg and 150 mg once daily.

Secondary Outcome Measures

Safety and tolerability of 3TC following the administration of 3TC 300 mg and 150 mg once daily

Full Information

NCT ID

NCT00985647

First Posted

September 25, 2009

Last Updated

February 9, 2011

Sponsor

Kirby Institute

1. Study Identification

Unique Protocol Identification Number

NCT00985647

Brief Title

Pharmacokinetics of Lamivudine at Two Different Doses

Acronym

ENCORE2

Official Title

Pharmacokinetics of Plasma Lamivudine (3TC), and Its Active Intracellular Anabolite 3TC-Triphosphate Over a 24 Hour Dosing Interval Following Administration of 3TC 300 mg and 150 mg Once Daily to HIV-Negative Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

February 2011

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Kirby Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of the study is to measure the pharmacokinetics (how a drug is absorbed, distributed and eliminated from the body) of lamivudine (3TC) and its active component after 3TC is given at two different doses, 300mg and 150mg once daily.

Detailed Description

Lamivudine (3TC) has been approved by regulatory authorities for the treatment of HIV infection and the current licensed dose is 300 mg once daily. Clinical and pharmacokinetic (how a drug is absorbed, distributed and eliminated from your body) data suggest that the licensing dose could be reduced without compromising effectiveness. Lower drug doses could reduce the side-effects from the medication and would make 3TC more affordable. This study will compare the pharmacokinetics, safety and tolerability of two different doses of 3TC in healthy volunteers. The study will take place at Chelsea and Westminster Hospital. Twenty four healthy HIV negative volunteers will be randomly allocated into two groups. Volunteers in Group 1 will start 300mg 3TC once daily for 10 days, followed by 10 days of not taking any 3TC (wash-out period). When the wash-out period ends, they will re-start 3TC at a dose of 150mg once daily for 10 days. Group 2 is similar except that they will start 150mg 3TC at the beginning of the study and 300mg 3TC after the wash-out period. Blood samples will be taken over a 24-hour period at the end of each dosing phase to measure the levels of 3TC in the blood and inside blood cells. Safety and tolerability of 3TC will be assessed by questions, physical examination and laboratory parameters. These will be performed at regular intervals during the treatment phases. Healthy participants as determined by their medical history and physical examination will be eligible to participate in the study. HIV-positive participants will not be recruited because it is not yet clear if an experimentally reduced dose of 3TC will successfully treat HIV-infection. There is no reason to presume that there is any meaningful difference in the metabolic processing of 3TC 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

HIV Infections

Keywords

HIV, HAART, ART, Pharmacokinetic, Healthy volunteers, 3TC, Lamivudine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

3TC 300mg/150mg

Arm Type

Active Comparator

Arm Description

Arm Title

3TC 150mg/300mg

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lamivudine (3TC)

Other Intervention Name(s)

Epivir

Intervention Description

3TC 300mg/150mg participants will receive 3TC 300 mg (2 x 150 mg tablet) once daily for 10 days, washout for 10 days and then 3TC 150 mg (1 x 150 mg tablet) once daily for 10 days. 3TC 150mg/300mg participants will receive 3TC 150 mg (1 x 150 mg tablet) once daily for 10 days, washout for 10 days and then 3TC 300 mg (2 x 150 mg tablet) once daily for 10 days.

Primary Outcome Measure Information:

Title

Plasma concentrations of 3TC and intracellular concentrations of its active anabolite 3TC-TP as measured by the Area Under the Curve (AUC 0-24h).

Description

Concentrations will be compared after the administration of 3TC 300 mg and 150 mg once daily.

Time Frame

Measured over 24 hours at the end of each 10-day dosing period.

Secondary Outcome Measure Information:

Title

Safety and tolerability of 3TC following the administration of 3TC 300 mg and 150 mg once daily

Time Frame

Assessed at regular intervals throughout the study

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: 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 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 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

Country

United Kingdom

12. IPD Sharing Statement

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Pharmacokinetics of Lamivudine at Two Different Doses

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