Lamivudine and Adefovir Dipivoxil Fixed Dose Combination
A Randomized, Open-label, Single-dose, Two-period, Crossover Study to Demonstrate the Bioequivalence of the Fixed Dose Combination (FDC) of Lamivudine and Adefovir Dipivoxil (100mg/10mg) to Heptodin® (100mg ) and Hepsera® (10mg)
1 other identifier
interventional
40
1 country
1
Brief Summary
This is a phase I study being conducted to support the clinical development program of a FDC product of the nucleoside analogue lamivudine and the nucleotide analogue adefovir dipivoxil. To establish bioequivalence, the exposure of lamivudine and adefovir dipivoxil when administered as the FDC will be compared to that of Heptodin (lamivudine) and Hepsera (adefovir dipivoxil) when administered separately. In this study, the FDC product will contain 100mg lamivudine/10mg adefovir dipivoxil. Total 40 healthy adult subjects will be enrolled. The study will include a screening visit and two treatment sessions. The screening visit will be conducted up to 3 weeks prior to the first dose of Session 1. All subjects will receive Regimen A through B according to the randomization schedule. Eligible subjects will be enrolled in the study and randomized to receive the following treatment regimens in table below in one of the following treatment sequences: AB, or BA. There will be a seven to ten days washout period between each treatment session. Pharmacokinetic sampling for measurement of plasma lamivudine and adefovir dipivoxil concentrations will be conducted over a 48-hour period following the morning administration of study medication in each study session. During this time, all subjects will remain in the unit for pharmacokinetic (PK) sample collection. The total duration (from screening to the end of the study) of each subject's participation will be approximately four weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2011
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 21, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 12, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
April 12, 2011
CompletedFirst Submitted
Initial submission to the registry
May 5, 2011
CompletedFirst Posted
Study publicly available on registry
May 16, 2011
CompletedAugust 4, 2017
August 1, 2017
2 months
May 5, 2011
August 2, 2017
Conditions
Outcome Measures
Primary Outcomes (4)
AUC of lamivudine
48 hours
Cmax of lamivudine
48 hours
AUC of adefovir dipivoxil
48 hours
Cmax of adefovir dipivoxil
48 hours
Secondary Outcomes (5)
PK parameters: t1/2 of lamivudine
48 hours
Tolerability will be assessed by clinical data from Adverse Event reporting, nurse/physician observations, vital signs, ECGs, and clinical laboratory.
48 hours
PK parameters: Tmax of lamivudine
48 hours
PK parameters: Tmax of adefovir dipivoxil
48 hours
PK parameters: t1/2 of adefovir dipivoxil
48 hours
Study Arms (2)
Lamivudine and Adefovir dipivoxil
ACTIVE COMPARATOROne 100mg Lamivudine tablet and One 10mg Adefovir dipivoxil tablet
Fixed dose combination
EXPERIMENTALOne capsule (100mg lamivudine and 10mg adefovir dipivoxil)
Interventions
100mg/10mg capsule
Eligibility Criteria
You may qualify if:
- 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%).
You may not qualify if:
- 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).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (1)
GSK Investigational Site
Shatin, New Territories, Hong Kong
Related Publications (1)
Fok BS, Gardner S, Piscitelli S, Chen S, Chu TT, Chan JC, Tomlinson B. Pharmacokinetic properties of single-dose lamivudine/adefovir dipivoxil fixed-dose combination in healthy Chinese male volunteers. Clin Ther. 2013 Jan;35(1):68-76. doi: 10.1016/j.clinthera.2012.12.001. Epub 2012 Dec 28.
PMID: 23274144BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 5, 2011
First Posted
May 16, 2011
Study Start
February 21, 2011
Primary Completion
April 12, 2011
Study Completion
April 12, 2011
Last Updated
August 4, 2017
Record last verified: 2017-08
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.