Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to compare the rate and extent of absorption of venlafaxine hydrochloride 150 mg capsules (test) versus Effexor® XR (reference) administered as the content of 1 x 150 mg extended-release capsule mixed with applesauce under fasting conditions.
Interventions
150 mg Extended-Release Capsule
DRUGEffexor® XR
150 mg Extended-Release Capsule
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Members of the community at large. * Subjects will be females and/or males, non-smokers, 18 years of age and older. * Female subjects will be postmenopausal or surgically sterilized.
Exclusion criteria
* Clinically significant illness within 4 weeks of the administration of study medication. * Clinically significant surgery within 4 weeks prior to the administration of the study medication. * Any clinically significant abnormality found during medical screening. * Any reason which, in the opinion of the medical sub-investigator, would prevent the subject from participating in the study. * Abnormal laboratory tests judged clinically significant. * Positive urine drug screen at screening. * Positive testing for hepatitis B, hepatitis C, or HIV at screening. * ECG abnormalities (clinically significant) or vital sign abnormalities at screening. * Subjects with BMI greater than 30.0. * History of significant alcohol abuse within 6 months of the screening visit or any indication of the regular use of more than 14 units of alcohol per week (1 unit is equal to 150 mL of wine, 360mL of beer, or 45 mL of alcohol 40%). * 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, PCP, crack) within 1 year of the screening visit. * History of allergic reactions to venlafaxine. * History of allergic reactions to heparin. * Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to administration of the study medication. * Use of an investigational drug or participation in an investigational study within 30 days prior to administration of the study medication. * History or presence of any clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug. * Any 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 within 7 days prior to administration of study medication, except for topical products without systemic exposure. * Positive alcohol breath test at screening. * Subjects who have used tobacco in any form within the 90 days preceding study drug administration. * Any food allergies, intolerance, restriction, or special diet that, in the opinion of the medical sub-investigator, contraindicates the subject's participation in this study. * Subjects who have had a depot injection or implant of any drug 3 months prior to administration of study medication. * Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follows: * less than 300 mL of whole blood within 30 days or * 300 mL to 500 mL of whole blood within 45 days or * more than 500 mL of whole blood within 56 days. * Subjects who have consumed food or beverages containing grapefruit within 7 days prior to administration of the study medication. * Subjects with clinically significant presence or history of raised intra-ocular pressure or at the risk of acute narrow angle glaucoma. * Subjects who have dentures or braces. * Intolerance to venipunctures. * Subjects with a clinically significant history of tuberculosis, epilepsy, asthma, diabetes, or psychosis will not be eligible for this study. * Subjects who are unable to understand or unwilling to sign the Informed Consent Form. * Subjects with the known presence of volume-depletion. * Subjects predisposed to bleeding of the skin and mucous membrane (impaired platelet aggregation). * Subjects with clinically significant history of seizures. * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Venlafaxine. | Blood samples collected over a 48 hour period. | Bioequivalence based on Venlafaxine Cmax (maximum observed concentration of drug substance in plasma). |
| AUC0-t of Venlafaxine. | Blood samples collected over a 48 hour period. | Bioequivalence based on Venlafaxine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration). |
| AUC0-inf of Venlafaxine. | Blood samples collected over a 48 hour period. | Bioequivalence based on Venlafaxine AUC0-inf (area under the concentration-time curve from time zero to infinity). |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Venlafaxine Hydrochloride (Test) First 150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in first period followed by 150 mg Effexor® XR Capsules reference product dosed in the second period. | 12 |
| Effexor® XR (Reference) First 150 mg Effexor® XR Extended-Release Capsules reference product dosed in first period followed by 150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in the second period. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Emesis During Dosing Interval | 0 | 3 |
| Washout of 7 Days | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Venlafaxine Hydrochloride (Test) First | Effexor® XR (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 11 participants | 12 participants | 23 participants |
| Region of Enrollment Canada | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 10 Participants | 9 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 | 16 / 24 | 9 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
AUC0-inf of Venlafaxine.
Bioequivalence based on Venlafaxine AUC0-inf (area under the concentration-time curve from time zero to infinity).
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Hydrochloride (Test) | AUC0-inf of Venlafaxine. | 2163.77 ng*h/mL | Standard Deviation 1647.47 |
| Effexor® XR (Reference) | AUC0-inf of Venlafaxine. | 2065.50 ng*h/mL | Standard Deviation 1626.52 |
90% CI: [101.45, 111.71]
Primary
AUC0-t of Venlafaxine.
Bioequivalence based on Venlafaxine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Hydrochloride (Test) | AUC0-t of Venlafaxine. | 1972.77 ng*h/mL | Standard Deviation 1425.56 |
| Effexor® XR (Reference) | AUC0-t of Venlafaxine. | 1800.03 ng*h/mL | Standard Deviation 1270.77 |
90% CI: [103.68, 116.63]
Primary
Cmax of Venlafaxine.
Bioequivalence based on Venlafaxine Cmax (maximum observed concentration of drug substance in plasma).
Time frame: Blood samples collected over a 48 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Hydrochloride (Test) | Cmax of Venlafaxine. | 120.07 ng/mL | Standard Deviation 45.48 |
| Effexor® XR (Reference) | Cmax of Venlafaxine. | 103.59 ng/mL | Standard Deviation 39.47 |
90% CI: [108.45, 123.72]