Last updated: 11/07/2018 08:26:39
Lamivudine and Adefovir Dipivoxil Fixed Dose Combination
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: 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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
AUC of lamivudine
Timeframe: 48 hours
Cmax of lamivudine
Timeframe: 48 hours
AUC of adefovir dipivoxil
Timeframe: 48 hours
Cmax of adefovir dipivoxil
Timeframe: 48 hours
Secondary outcomes:
PK parameters: t1/2 of lamivudine
Timeframe: 48 hours
Tolerability will be assessed by clinical data from Adverse Event reporting, nurse/physician observations, vital signs, ECGs, and clinical laboratory.
Timeframe: 48 hours
PK parameters: Tmax of lamivudine
Timeframe: 48 hours
PK parameters: Tmax of adefovir dipivoxil
Timeframe: 48 hours
PK parameters: t1/2 of adefovir dipivoxil
Timeframe: 48 hours
Interventions:
Enrollment:
40
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Chen, Shuguang ; CM Chan, Jones ; Gardner, Stephen ; Piscitelli, Stephen ; SP Fok, Benny ; Tomlinson, Brian ; TW Chu, Tanyai. Pharmacokinetic Properties of Single-Dose Lamivudine/Adefovir Dipivoxil Fixed-Dose Combination in Healthy Chinese Male Volunteers. [Clin Ther]. 2012;12(001):9.
Medical condition
Hepatitis B, Chronic
Product
adefovir, adefovir/lamivudine, lamivudine
Collaborators
Not applicable
Study date(s)
February 2011 to April 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
- Healthy as determined by a responsible physician.
- Male 18 and 55 years of age.
- 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.
Inclusion and exclusion criteria
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).
- 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
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).
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-12-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereResults for study 114957 can be found on the GSK Clinical Study Register.
Click hereAccess to clinical trial data by researchers
Visit website