Healthy
Conditions
Brief summary
The objective of this study was to compare the rate and extent of absorption of Teva Pharmaceuticals USA valacyclovir and GlaxoSmithKline, USA (Valtrex) valacyclovir, administered as 1 x 1000 mg tablet under fed conditions.
Interventions
DRUGValacyclovir
Test 1000 mg Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female, non-smokers, 18 years of age and older. * Capable of consent
Exclusion criteria
Subjects to whom any of the following applies will be excluded from the study: * Clinically significant illnesses or surgery within 4 weeks of the administration of study medication. * Any clinically significant abnormality found during medical screening. * Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study. * Abnormal laboratory tests judged clinically significant. * Positive testing for hepatitis B, hepatitis C or HIV at screening. * ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, or diastolic blood pressure lower than 50 or over 90 mmHg; or heart rate less than 50 or over 100 bpm) at screening. * BMI less than 19.0 or greater than or equal to 30.0 kg/m2. * History of significant alcohol abuse within six months prior to the screening visit (more than fourteen units of alcohol per week \[1 Unit = 150 mL of wine or 360 mL of beer or 45 mL of alcohol 40% alcohol\]) or positive urine drug screen at screening. * History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within 1 year prior to the screening visit or positive urine drug screen at screening. * History of allergic reactions to heparin, valacyclovir, acyclovir, or other related drugs. * Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of inhibitors: antidepressants (SSRI), cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to the administration of the study medication. * Use of an investigational drug or participation in an investigation study within 30 days prior to the administration of the study medication. * Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug. * Any clinically significant history or presence of clinically significant neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease. * Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption. * Difficulty to swallow study medication. * Use of any tobacco products in the 90 days preceding drug administration. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the medical subinvestigator, could contraindicate the subjects participation in this study. * A depot injection or an implant of any drug within 3 months prior to administration of study medication. * Donation of plasma (500 mL) within 30 days prior to drug administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the screening procedures of this study) prior to administration of the study medication as follows: * 50 mL to 300 mL of whole blood within 30 days, * 301 mL to 500 mL of whole blood within 45 days, or * more than 500 mL of whole blood within 56 days prior to drug administration. * Intolerance to venipunctures. * Clinically significant history of renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study. * Unable to understand or unwilling to sign the Informed Consent Form. * Breast-feeding. * Positive urine pregnancy test at screening. * Female subjects of childbearing potential having unprotected sexual intercourse with any non-sterile male partner (i.e. male who has not been sterilized by vasectomy for at least 6 months) within 14 days prior to study drug administration. Acceptable methods of contraception: * Intra-uterine contraceptive device (placed at least 4 weeks prior to study drug administration), * Condom or diaphragm + spermicide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Valacyclovir | Blood samples collected over 12 hour period | Bioequivalence based on Cmax |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Valacyclovir | Blood samples collected over 12 hour period | Bioequivalence based on AUC0-t |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Valacyclovir | Blood samples collected over 12 hour period | Bioequivalence based on AUC0-inf |
Secondary
| Measure | Time frame |
|---|---|
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Acyclovir | Blood samples collected over 24 hour period |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Acyclovir | Blood samples collected over 24 hour period |
| AUC0-t (Area Under Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Acyclovir | Blood samples collected over 24 hour period |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valacyclovir Test 1000 mg Tablet dosed in first period follwed by Reference Listed 1000 mg Valtrex® tablet in second period | 18 |
| Valtrex® Reference Listed Valtrex® 1000 mg Tablet dosed in first period followed by Test 1000 mg Valacyclovir tablet in second period | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Valtrex® | Valacyclovir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 18 Participants | 35 Participants |
| Race/Ethnicity, Customized Caucasian | 18 Participants | 18 Participants | 36 Participants |
| Region of Enrollment Canada | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 36 | 10 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Valacyclovir
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 12 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Valacyclovir | 552.17 ng*h/mL | Standard Deviation 138.76 |
| Valtrex® | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Valacyclovir | 554.53 ng*h/mL | Standard Deviation 140.97 |
90% CI: [96.38, 103.78]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Valacyclovir
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 12 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Valacyclovir | 549.32 ng*h/mL | Standard Deviation 137.87 |
| Valtrex® | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Valacyclovir | 551.77 ng*h/mL | Standard Deviation 140.73 |
90% CI: [96.34, 103.82]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Valacyclovir
Bioequivalence based on Cmax
Time frame: Blood samples collected over 12 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Valacyclovir | 385.35 ng/mL | Standard Deviation 139.1 |
| Valtrex® | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Valacyclovir | 350.86 ng/mL | Standard Deviation 133.2 |
90% CI: [100.54, 123.29]
Secondary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Acyclovir
Time frame: Blood samples collected over 24 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Acyclovir | 22705.17 ng*h/mL | Standard Deviation 4336.16 |
| Valtrex® | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) - Acyclovir | 22887.99 ng*h/mL | Standard Deviation 4065.19 |
90% CI: [97.04, 101.19]
Secondary
AUC0-t (Area Under Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Acyclovir
Time frame: Blood samples collected over 24 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | AUC0-t (Area Under Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Acyclovir | 22514.36 ng*h/mL | Standard Deviation 4316.76 |
| Valtrex® | AUC0-t (Area Under Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) - Acyclovir | 22675.85 ng*h/mL | Standard Deviation 4063.2 |
90% CI: [97.14, 101.31]
Secondary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Acyclovir
Time frame: Blood samples collected over 24 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Acyclovir | 6485.51 ng/mL | Standard Deviation 1469.43 |
| Valtrex® | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) - Acyclovir | 6283.25 ng/mL | Standard Deviation 1375.42 |
90% CI: [97.87, 109.41]