Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this single-dose, open-label, randomized, two-period crossover study was to compare the rate of absorption and oral bioavailability of a test formulation of doxycycline monohydrate 1 x 25 mg (5mL) oral suspension manufactured by IVAX Pharmaceuticals, Inc. and distributed by TEVA Pharmaceuticals USA to an equivalent oral dose of the commercially available reference product, Vibramycin Monohydrate® manufactured by Pfizer, Inc. following an overnight fast of at least 10 hours.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
25 mg 5 mL dose
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
All subjects must satisfy the following criteria to be considered for study participation: * Subject must be male or non-pregnant, non-breast-feeding female * Subject must be at least 18 years of age * Subject must have a Body Mass Index (BMI) between 18 and 30 kg/m2, inclusive, and body weight should be at least 50 kg (110 lbs) * Female Subjects - not surgically sterile or at least two years postmenopausal - must agree to utilize one of the following forms of contraception, if sexually active with a male partner, from screening through completion of the study. Approved forms of contraception are abstinence, double barrier (condom with spermicide, diaphragm with spermicide), intra-uterine device (IUD), or vasectomized partner (6 months minimum since vasectomy). * Subject must voluntarily consent to participate in this study and provide their written informed consent prior to the start of any study-specific procedures. * Subject is willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during each study period. * Subject is willing and able to remain in the study unit for the entire duration of each confinement period and return for any outpatient visits.
Exclusion criteria
Subjects may be excluded for any of the following: * History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. * Has a clinically significant abnormal finding on the physical exam, medical history, ECG or clinical laboratory results at screening. * History or presence of allergic or adverse response to doxycycline monohydrate or related drugs. * Has been on a significantly abnormal diet during the four weeks preceding the first dose of study medication. * Has donated blood or plasma within 30 days prior to the first dose of study medication. * Has participated in another clinical trial within 30 days prior to the first dose of study medication. * Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication. * Has used any prescription medication, including hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication. * Has been treated with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication. * Has smoked or used tobacco products within 90 days prior to the first dose of study medication. * Is a female with a positive pregnancy test result. * Has an intolerance to venipuncture. * Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) * Has a history of drug or alcohol abuse. * Has had a positive test for, or has been treated for hepatitis B, hepatitis C or HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax = Maximum Observed Concentration. | Blood samples collected over a 72 hour period. | Bioequivalence based on Cmax. |
| AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration. | Blood samples collected over a 72 hour period. | Bioequivalence based on AUC0-t. |
| AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | Blood samples collected over a 72 hour period. | Bioequivalence based on AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline Monohydrate First 25mg(5mL)Doxycycline Monohydrate Oral Suspension test product dosed in first period followed by 25mg(5mL) Vibramycin® Monohydrate Oral Suspension reference product dosed in the second period. | 15 |
| Vibramycin® Monohydrate First 25mg(5mL) Vibramycin® Monohydrate Oral Suspension reference product dosed in first period followed by 25mg(5mL) Doxycycline Monohydrate Oral Suspension test product dosed in the second period. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| First Intervention | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Doxycycline Monohydrate First | Vibramycin® Monohydrate First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 14 Participants | 29 Participants |
| Race/Ethnicity, Customized Black | 2 participants | 5 participants | 7 participants |
| Race/Ethnicity, Customized Hispanic | 7 participants | 7 participants | 14 participants |
| Race/Ethnicity, Customized White | 6 participants | 3 participants | 9 participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 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 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline Monohydrate | AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | 6195 ng*h/mL | Standard Deviation 1437 |
| Vibramycin® Monohydrate | AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | 6250 ng*h/mL | Standard Deviation 1288 |
90% CI: [94.78, 102.28]
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 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline Monohydrate | AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration. | 5769 ng*h/mL | Standard Deviation 1327 |
| Vibramycin® Monohydrate | AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration. | 5870 ng*h/mL | Standard Deviation 1225 |
90% CI: [93.98, 101.67]
Primary
Cmax = Maximum Observed Concentration.
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline Monohydrate | Cmax = Maximum Observed Concentration. | 363 ng/mL | Standard Deviation 105 |
| Vibramycin® Monohydrate | Cmax = Maximum Observed Concentration. | 383 ng/mL | Standard Deviation 96.5 |
90% CI: [88.49, 98.83]