Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to evaluate the comparative bioavailability between pravastatin sodium 80 mg tablets (Distributed by Teva Pharmaceuticals, USA) and Pravachol® 80 mg tablets (Bristol Myers Squibb, USA), after a single-dose in healthy subjects under fasting conditions.
Detailed description
Detailed Description Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods Outcome: Confidence interval fell within 80-125% therefore met the FDA Bioequivalence criteria; no drug related, serious, unexpected adverse events were reported during the study.
Interventions
DRUGPravastatin sodium 80 mg tablets
1 x 80 mg
DRUGPravachol® 80 mg tablets
1 x 80 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 greater than or equal to 19 and less than or equal to 30. * Negative for: * HIV. * Hepatitis B surface antigen and Hepatitis C antibody. * Using drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). * Urine cotinine test * 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: * unable to have children (e.g. post-menopausal, tubal ligation, hysterectomy or, * willing to remain abstinent \[not engage in sexual intercourse\] or, * willing to use an effective method of double-barrier birth control \[partner using condom and female using diaphragm, contraceptive sponge, spermicide or IUD\]. * Females who participate in this study are non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * Known history or presence of: * Hypersensitivity or idiosyncratic reaction to pravastatin sodium and/or any other drug substances with similar activity. * Alcoholism within the last 12 months. * Drug dependence and/or substance abuse. * 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 500 mL of blood in the previous 45 days OR Donated more than 500 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) 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 - Pravastatin in Plasma | Blood samples collected over 16 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 16 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 16 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pravastatin (Test) First Pravastatin 80 mg Tablet (test) dosed in first period followed by Pravachol® 80 mg Tablet (reference) dosed in second period | 30 |
| Pravachol® (Reference) First Pravachol® 80 mg Tablet (reference) dosed in first period followed by Pravastatin 80 mg Tablet (test) dosed in second period | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| Washout: 7 Days | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Pravastatin (Test) First | Pravachol® (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 | 30 Participants | 30 Participants | 60 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Caucasian | 21 Participants | 22 Participants | 43 Participants |
| Region of Enrollment Canada | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 15 Participants | 17 Participants | 32 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 16 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 409.224 ng*h/mL | Standard Deviation 199.894 |
| Pravachol® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 378.930 ng*h/mL | Standard Deviation 206.667 |
90% CI: [104.31, 116.96]
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 16 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 404.202 ng*h/mL | Standard Deviation 199.159 |
| Pravachol® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 373.720 ng*h/mL | Standard Deviation 204.837 |
90% CI: [104.39, 117.2]
Primary
Cmax - Maximum Observed Concentration - Pravastatin in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 16 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Cmax - Maximum Observed Concentration - Pravastatin in Plasma | 191.857 ng/mL | Standard Deviation 109.746 |
| Pravachol® | Cmax - Maximum Observed Concentration - Pravastatin in Plasma | 188.460 ng/mL | Standard Deviation 123.226 |
90% CI: [98.17, 113.93]