Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to compare the single-dose relative bioavailability of TEVA and Aventis Pharmaceuticals (DDAVP®) 0.2 mg desmopressin acetate tablets following a 0.8 mg dose under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
4 x 0.2 mg, single-dose fasting
DRUGDDAVP® 0.2 mg Tablets
4 x 0.2 mg, single-dose fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult non-smoker (for at least 3 months) or light smoking (less than 10 cigarettes per day for at least 3 months) male or female subjects, 18-55 years of age; * Weighing at least 60 kg for males and 52 kg for females; * Subjects who had a body mass index (BMI) less than 30; * Medically healthy subjects with clinically normal laboratory profiles and ECGs; Females of childbearing potential should have either been sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or have been using one of the following acceptable birth control methods: * surgically sterile (tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum. Proof was required for the hysterectomy and oophorectomy; * IUD in place for at least 3 months; * barrier methods (condom, diaphragm) with spermicide for at least 14 days prior to the first dose and throughout the study; * surgical sterilization of the partner (vasectomy for 6 months minimum); * hormonal contraceptives for at least 3 months prior to the first dose of the study. Other birth control methods were deemed acceptable. Postmenopausal women with amenorrhea for at least 2 years were eligible. * Voluntarily consent to participate in the study.
Exclusion criteria
* Female subjects who were pregnant or lactating. * Subjects who had been on a special diet (for whatever reason) during the 28 days prior to the first dose and throughout the study. * Any clinically significant illness within 4 weeks prior to dosing. * Subjects with any medical condition requiring regular treatment with prescription drugs. * The use of any pharmacological agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days prior to the first dose. * Subjects who, through completion of the study, would have donated in excess of: 500 mL of blood and/or plasma in 14 days; 1500 mL of blood and/or plasma in 180 days; 2500 mL of blood and/or plasma in 1 year. * Subjects who had donated plasma within 30 days prior to the first dose. * Subjects who ahd participated in another clinical trial within 30 days prior to the first dose. * Subjects who did not tolerate venipuncture. * History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. In addition, the history or presence of: * hypersensitivity or idiosyncratic reaction to desmopressin or any other synthetic anti-diuretic hormones; * type IIB von Willebrand's disease; * personal or family bleeding disorder; * alcoholism or drug abuse within the past year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 12 hour period | Bioequivalence based on Cmax |
| AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 12 hour period | Bioequivalence based on AUCinf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 12 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Desmopressin Acetate Desmopressin Acetate 4 x 0.2 mg Tablet (test) dosed in first period followed by DDAVP® 4 x 0.2 mg Tablet (reference) dosed in second period | 24 |
| DDAVP® DDAVP® 4 x 0.2 mg Tablet (reference) dosed in first period followed by Desmopressin Acetate 4 x 0.2 mg Tablet (test) dosed in second period | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 0 | 1 |
| Washout: 7 Days | Adverse Event | 2 | 1 |
| Washout: 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Desmopressin Acetate | DDAVP® | 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 | 24 Participants | 24 Participants | 48 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 22 Participants | 20 Participants | 42 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Canada | 24 participants | 24 participants | 48 participants |
| Sex: Female, Male Female | 12 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 30 Participants |
Outcome results
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
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 |
|---|---|---|---|
| Desmopressin Acetate | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 252.85 pg*h/mL | Standard Deviation 162.914 |
| DDAVP® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 268.02 pg*h/mL | Standard Deviation 188.907 |
90% CI: [87.7, 106.1]
Primary
AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUCinf
Time frame: Blood samples collected over 12 hour period
Population: AUC0-inf could not be estimated for one subject in the reference arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Desmopressin Acetate | AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 266.62 pg*h/mL | Standard Deviation 169.435 |
| DDAVP® | AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 286.34 pg*h/mL | Standard Deviation 199.268 |
90% CI: [86.9, 105.2]
Primary
Cmax - Maximum Observed Concentration
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 |
|---|---|---|---|
| Desmopressin Acetate | Cmax - Maximum Observed Concentration | 78.102 pg/mL | Standard Deviation 52.5437 |
| DDAVP® | Cmax - Maximum Observed Concentration | 82.888 pg/mL | Standard Deviation 64.2238 |
90% CI: [87.8, 108.3]