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Pharmacokinetics of Lamivudine at Two Different Doses (ENCORE2)

This study has been completed.
Sponsor:
Information provided by:
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00985647
First received: September 25, 2009
Last updated: February 9, 2011
Last verified: February 2011

September 25, 2009
February 9, 2011
December 2009
February 2010   (final data collection date for primary outcome measure)
Plasma concentrations of 3TC and intracellular concentrations of its active anabolite 3TC-TP as measured by the Area Under the Curve (AUC 0-24h). [ Time Frame: Measured over 24 hours at the end of each 10-day dosing period. ] [ Designated as safety issue: No ]
Concentrations will be compared after the administration of 3TC 300 mg and 150 mg once daily.
Steady state plasma concentrations of 3TC and intracellular concentrations of its active anabolite 3TC‐TP following the administration of 3TC 300 mg and 150 mg once daily [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00985647 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: Yes ]
Safety and tolerability of 3TC following the administration of 3TC 300 mg and 150 mg once daily [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Pharmacokinetics of Lamivudine at Two Different Doses
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
Drug: Lamivudine (3TC)

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.

Other Name: Epivir
  • Active Comparator: 3TC 300mg/150mg
    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
    Intervention: Drug: Lamivudine (3TC)
  • Active Comparator: 3TC 150mg/300mg
    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
    Intervention: Drug: Lamivudine (3TC)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
March 2010
February 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  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 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. 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
  9. 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
  10. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00985647
NCHECR-ENCORE2
Yes
Marta Boffito, HIV/GUM Research Unit
Kirby Institute
Not Provided
Principal Investigator: Marta Boffito, MD PhD Chelsea and Westminster Hospital
Kirby Institute
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP