Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
This study will compare the relative bioavailability (rate and extent of absorption) of 15 mg Mirtazapine (Orally Disintegrating) Tablets manufactured by TEVA Pharmaceutical Industries, Ltd.; distributed by TEVA Pharmaceuticals USA with that of 15 mg REMERON SolTab® Orally Disintegrating Tablets manufactured for Organon Inc. by CIMA Labs Inc. following a single oral dose (1 x 15 mg) in healthy adult subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 15 mg, single-dose fasting
1 x 15 mg, single-dose fasting
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
* Screening Demographics: All subjects selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be less than or equal to 30. * Screening Procedures: Each subject will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before fill implementation of screening procedures. * Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems. * The screening clinical laboratory will include: * Hematology: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count; * Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase; * HIV antibody, hepatitis B surface antigen, and hepatitis C antibody screens; * Urinalysis: by dipstick; full microscopic examination of dipstick positive; and * Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine. * Serum Pregnancy Screen (female subjects only) * If female and: * of childbearing potential, is practicing an acceptable barrier method of birth control for the duration of the study as judged by the investigator(s), such as condoms, sponge, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence; or * is postmenopausal for at least 1 year; or * is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Exclusion criteria
* Subjects with a recent history of drug or alcohol addiction or abuse. * Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators). * Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant. * Subjects demonstrating a positive hepatitis B surface antigen screen, hepatitis C antibody screen, or a reactive HIV antibody screen. * Subjects demonstrating a positive pregnancy screen. * Subjects who are currently breastfeeding. * Subjects with a history of clinically significant allergies including drug allergies. * Subjects with a history of allergic response(s) to mirtazapine or related drugs. * Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators). * Subjects who currently use of have used tobacco products within 90 days of Period I dosing. * Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing. * Subjects who report donating greater than 150 mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study. * Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study. * Subjects who report receiving any investigational drug within 28 days prior to Period I dosing. * Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing. * Subjects who report an intolerance of direct venipuncture. * Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 120 hour period. | Bioequivalence based on AUC0-t. |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 120 hour period. | Bioequivalence based on Cmax. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 120 hour period. | Bioequivalence based on AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Mirtazapine) First 15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in first period followed by 15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in the second period. | 16 |
| Reference (Remeron®) First 15 mg Remeron® SolTab™ Orally Disintegrating Tablets reference product dosed in first period followed by 15 mg Mirtazapine Orally Disintegrating Tablets test product dosed in the second period. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 14 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Test (Mirtazapine) First | Reference (Remeron®) 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 | 16 Participants | 16 Participants | 32 Participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 16 participants | 15 participants | 31 participants |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 120 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Mirtazapine) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 327022.65 pg*h/mL | Standard Deviation 109980.75 |
| Reference (Remeron®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 316863.06 pg*h/mL | Standard Deviation 111509.8 |
90% CI: [99.47, 108.46]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 120 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Mirtazapine) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 303749.52 pg*h/mL | Standard Deviation 104877.35 |
| Reference (Remeron®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 294920.42 pg*h/mL | Standard Deviation 105344.06 |
90% CI: [99.13, 108.25]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 120 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Mirtazapine) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 32975.95 pg/mL | Standard Deviation 11873.83 |
| Reference (Remeron®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 33122.52 pg/mL | Standard Deviation 11246.45 |
90% CI: [92.84, 106.69]