Lamivudine and Adefovir Dipivoxil Fixed Dose Combination

This is an interventional treatment trial for Hepatitis B, Chronic Read More

Inclusion Criteria:

• Healthy as determined by a responsible physician.
• Male 18 and 55 years of age.
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods.
• Body weight >50 kg (110 lbs) and body mass index (BMI) between 19.0 and 25.0.
• Capable of giving written informed consent.
• QT interval corrected according to Bazzett's formula (QTcB) or QT interval corrected according to Fridericia's formula (QTcF) <450 msec; or QTc <480 msec in subjects with Bundle Branch Block.
• AST, ALT, alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Exclusion Criteria:

• Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or any other medical condition or circumstance making the subject unsuitable for participation in the study.
• Treatment with any prescription or non-prescription drugs (including vitamins, herbal and dietary supplements, as well as grapefruit-containing products) within 7 days or five half-lives prior to first dose of study medication and until the end of the study. Excluded from this list is acetaminophen at doses of <=2 grams/day.
• Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding Day 1 of treatment period 1.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.
• Positive urine drug screen (UDS) or breath alcohol test at screening. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• Positive for hepatitis B, hepatitis C or HIV.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Electrocardiogram findings as follows (a single repeat is allowed for eligibility determination):

Parameter Males Heart rate <45 and >100 beats per minute PR Interval <120 and >220 msec QRS duration <70 and >120 msec QTc interval (Bazett) >450 msec

• Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization).
• Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrio-ventricular block [second degree or higher], Wolf Parkinson White syndrome).
• Sinus pauses >3 seconds.
• Any significant arrhythmia which, in the opinion of the principal Investigator and GlaxoSmithKline medical monitor, will interfere with the safety for the individual subject.

• Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

  • Documented history of low blood pressure (BP; average systolic BP<=90 mmHg and/or diastolic BP <=45 mm Hg) or blood pressure below these values at time of screening.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • History of asthma or chronic obstructive pulmonary disease.
  • History of sensitivity to heparin, heparin- induced thrombocytopenia, or sensitivity to any of the study medications or components thereof.
  • History of anaphylaxis or anaphylactic reactions or severe allergic responses to drugs.
  • History of angioedema.
  • Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent.
  • Subject is mentally or legally incapacitated