Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to evaluate the comparative bioavailability between Ursodiol 500 mg Tablets (test) and Urso Forte™ 500 mg Tablets (reference) after a single-dose in healthy subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGUrsodiol
Ursodiol Tablets, 500 mg
DRUGUrso Forte™
Urso Forte™ Tablets, 500 mg
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
* Healthy, non-smoking male and female subjects, 18 years of age or older. * BMI ≥ 19 and ≤ 30. * Negative for: 1. HIV. 2. Hepatitis B surface antigen and Hepatitis C antibody. 3. Using drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). 4. Urine cotinine test 5. Serum HCG consistent with pregnancy (females only) * No significant diseases or clinically significant findings in a physical examination. * No clinically significant abnormal laboratory values. * No clinically significant findings in vital signs measurements and a 12-lead electrocardiogram (ECG). * Be informed of the nature of the study and given written consent prior to receiving any study procedure. * Females who participate in this study are: 1. unable to have children (e.g. post-menopausal, tubal ligation, hysterectomy) OR 2. willing to remain abstinent \[not engage in sexual intercourse\] OR 3. willing to use an effective method of double-barrier birth control (e.g. partner using condom and female using diaphragm, contraceptive sponge, spermicide or IUD) * Females who participate in this study are not pregnant and/or non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * Known history or presence of: 1. Hypersensitivity or idiosyncratic reaction to ursodiol and/or any other drug substances with similar activity. 2. Alcoholism within the last 12 months. 3. Drug dependence and/or substance abuse. 4. Use of tobacco or nicotine-containing products within the last 6 months. * On a special diet within 4 weeks prior to drug administration (e.g. liquid, protein, raw food diet). * Participated in another clinical trial or received and investigational product within 30 days prior to drug administration. * Donated up to 250 mL of blood within the previous 30 days OR Donated from 251 to 499 mL of blood in the previous 45 days OR Donated more than 499 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation. * Females taking oral or transdermal hormonal contraceptives within 14 days preceding period 1 dosing. * Females having taken implanted or injected hormonal contraceptives within 6 months prior to period 1 dosing. * Requirement of any non-topical medication (prescription and/or over-the-counter, with systemic absorption) on a routine basis. * Difficulty fasting or consuming the standard meals. * Do not tolerate venipuncture. * Unable to read or sign the ICF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration - for Total Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours - for Total Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-72 |
| Cmax for Baseline Corrected Total Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-72 for Baseline Corrected Total Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-72 |
| Cmax for Unconjugated Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-72 for Unconjugated Ursodiol | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-72 |
| Cmax for Unconjugated Ursodiol - Baseline Corrected | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-72 for Unconjugated Ursodiol - Baseline Corrected | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-72 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ursodiol Ursodiol Tablets, 500 mg (test) dosed in first period followed by Urso Forte™ Tablets, 500 mg (reference) dosed in second period. | 40 |
| Urso Forte™ Urso Forte™ Tablets, 500 mg (reference) dosed in first period followed by Ursodiol Tablets, 500 mg (test) dosed in second period. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period: First Intervention | Adverse Event | 0 | 1 |
| Period: Second Intervention | Adverse Event | 1 | 0 |
| Period: Washout of 28 Days | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Ursodiol | Urso Forte™ | 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 | 40 Participants | 40 Participants | 80 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 10 Participants | 11 Participants | 21 Participants |
| Race/Ethnicity, Customized Caucasian | 26 Participants | 23 Participants | 49 Participants |
| Region of Enrollment Canada | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 20 Participants | 16 Participants | 36 Participants |
| Sex: Female, Male Male | 20 Participants | 24 Participants | 44 Participants |
Outcome results
Primary
AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours - for Total Ursodiol
Bioequivalence based on AUC0-72
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours - for Total Ursodiol | 76949.818 ng*h/mL | Standard Deviation 29582.802 |
| Urso Forte™ | AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours - for Total Ursodiol | 73342.048 ng*h/mL | Standard Deviation 32482.856 |
90% CI: [101, 112]
Primary
AUC0-72 for Baseline Corrected Total Ursodiol
Bioequivalence based on AUC0-72
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | AUC0-72 for Baseline Corrected Total Ursodiol | 71039.735 ng*h/mL | Standard Deviation 25782.013 |
| Urso Forte™ | AUC0-72 for Baseline Corrected Total Ursodiol | 68003.665 ng*h/mL | Standard Deviation 27591.922 |
90% CI: [100, 111]
Primary
AUC0-72 for Unconjugated Ursodiol
Bioequivalence based on AUC0-72
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | AUC0-72 for Unconjugated Ursodiol | 26739.080 ng*h/mL | Standard Deviation 15149.751 |
| Urso Forte™ | AUC0-72 for Unconjugated Ursodiol | 24303.192 ng*h/mL | Standard Deviation 11676.848 |
90% CI: [103, 117]
Primary
AUC0-72 for Unconjugated Ursodiol - Baseline Corrected
Bioequivalence based on AUC0-72
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | AUC0-72 for Unconjugated Ursodiol - Baseline Corrected | 24795.871 ng*h/mL | Standard Deviation 14561.991 |
| Urso Forte™ | AUC0-72 for Unconjugated Ursodiol - Baseline Corrected | 22948.483 ng*h/mL | Standard Deviation 10755.947 |
90% CI: [100, 115]
Primary
Cmax for Baseline Corrected Total Ursodiol
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | Cmax for Baseline Corrected Total Ursodiol | 4864.646 ng/mL | Standard Deviation 1910.294 |
| Urso Forte™ | Cmax for Baseline Corrected Total Ursodiol | 4954.583 ng/mL | Standard Deviation 2255.564 |
90% CI: [91.9, 111]
Primary
Cmax for Unconjugated Ursodiol
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | Cmax for Unconjugated Ursodiol | 4412.700 ng/mL | Standard Deviation 1714.737 |
| Urso Forte™ | Cmax for Unconjugated Ursodiol | 4475.406 ng/mL | Standard Deviation 2066.537 |
90% CI: [92.5, 111]
Primary
Cmax for Unconjugated Ursodiol - Baseline Corrected
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | Cmax for Unconjugated Ursodiol - Baseline Corrected | 4384.711 ng/mL | Standard Deviation 1716.444 |
| Urso Forte™ | Cmax for Unconjugated Ursodiol - Baseline Corrected | 4456.451 ng/mL | Standard Deviation 2066.59 |
90% CI: [92.2, 111]
Primary
Cmax - Maximum Observed Concentration - for Total Ursodiol
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursodiol | Cmax - Maximum Observed Concentration - for Total Ursodiol | 4946.800 ng/mL | Standard Deviation 1919.778 |
| Urso Forte™ | Cmax - Maximum Observed Concentration - for Total Ursodiol | 5026.891 ng/mL | Standard Deviation 2274.811 |
90% CI: [92.3, 111]