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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine (3TC)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

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). [ 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: December 2009
Study Completion Date: March 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00985647

Locations
United Kingdom
St Stephen's Centre, Chelsea and Westminster Hospital
London, United Kingdom
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: Marta Boffito, MD PhD Chelsea and Westminster Hospital
  More Information

No publications provided

Responsible Party: Marta Boffito, HIV/GUM Research Unit
ClinicalTrials.gov Identifier: NCT00985647     History of Changes
Other Study ID Numbers: NCHECR-ENCORE2
Study First Received: September 25, 2009
Last Updated: February 9, 2011
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Kirby Institute:
HIV
HAART
ART
Pharmacokinetic
Healthy volunteers
3TC
Lamivudine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Lamivudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014