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 fed 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 Post Dose - for 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 Total Ursodiol - Baseline Corrected | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-72 for Total Ursodiol - Baseline Corrected | 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 (Test) First Ursodiol Tablets, 500 mg (test) dosed in first period followed by UrsoForte™ Tablets, 500 mg (reference) dosed in second period. | 46 |
| Urso Forte™ (Reference) First Urso Forte™ Tablets, 500 mg (reference) dosed in first period followed by Ursodiol Tablets, 500 mg (test) dosed in second period. | 46 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period: Second Intervention | Protocol Violation | 1 | 0 |
| Period: Washout of 28 Days | Protocol Violation | 2 | 3 |
Baseline characteristics
| Characteristic | Ursodiol (Test) First | Urso Forte™ (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 | 46 Participants | 46 Participants | 92 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 13 Participants | 11 Participants | 24 Participants |
| Race/Ethnicity, Customized Caucasian | 31 Participants | 33 Participants | 64 Participants |
| Region of Enrollment Canada | 46 participants | 46 participants | 92 participants |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 33 Participants | 29 Participants | 62 Participants |
Outcome results
Primary
AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post Dose - 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 Post Dose - for Total Ursodiol | 84789.776 ng*h/mL | Standard Deviation 33376.08 |
| Urso Forte™ | AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post Dose - for Total Ursodiol | 87925.305 ng*h/mL | Standard Deviation 30085.315 |
90% CI: [92.2, 98.9]
Primary
AUC0-72 for Total 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 Total Ursodiol - Baseline Corrected | 77392.805 ng*h/mL | Standard Deviation 25146.096 |
| Urso Forte™ | AUC0-72 for Total Ursodiol - Baseline Corrected | 80992.000 ng*h/mL | Standard Deviation 22688.058 |
90% CI: [91.3, 98.7]
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 | 28543.339 ng*h/mL | Standard Deviation 21022.046 |
| Urso Forte™ | AUC0-72 for Unconjugated Ursodiol | 30951.831 ng*h/mL | Standard Deviation 16492.541 |
90% CI: [85.5, 95.9]
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 | 26921.471 ng*h/mL | Standard Deviation 17284.94 |
| Urso Forte™ | AUC0-72 for Unconjugated Ursodiol - Baseline Corrected | 29177.523 ng*h/mL | Standard Deviation 12620.441 |
90% CI: [85, 96.3]
Primary
Cmax for Total 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 Total Ursodiol - Baseline Corrected | 6659.969 ng/mL | Standard Deviation 2304.322 |
| Urso Forte™ | Cmax for Total Ursodiol - Baseline Corrected | 7363.215 ng/mL | Standard Deviation 2899.526 |
90% CI: [85.5, 99.5]
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 | 5818.644 ng/mL | Standard Deviation 2145.519 |
| Urso Forte™ | Cmax for Unconjugated Ursodiol | 6549.897 ng/mL | Standard Deviation 2681.097 |
90% CI: [83.1, 98.3]
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 | 5794.876 ng/mL | Standard Deviation 2147.27 |
| Urso Forte™ | Cmax for Unconjugated Ursodiol - Baseline Corrected | 6522.456 ng/mL | Standard Deviation 2679.132 |
90% CI: [83.1, 98.3]
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 | 6763.805 ng/mL | Standard Deviation 2305.341 |
| Urso Forte™ | Cmax - Maximum Observed Concentration - for Total Ursodiol | 7461.161 ng/mL | Standard Deviation 2922.024 |
90% CI: [85.8, 99.7]