Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this randomized, single-dose, two-way crossover evaluation is to compare the relative bioequivalence of a test carvedilol formulation (TEVA Pharmaceuticals USA) to and equivalent oral dose of the commercially available carvedilol (COREG®, SmithKline Beecham Pharmaceuticals) in a test population of 36 adult individuals under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 25 mg
1 x 25 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
* Sex: Male of Female; similar proportions of each preferred. * Age: At least 18 years. * Weight: Minimum of 120 pounds and a BMI (body mass index) of less than 30.
Exclusion criteria
* Subjects not complying with the above inclusion criteria must be excluded from the study. * In addition, any one of the conditions listed below will exclude a subject from the study. * History of treatment for alcoholism, substance abuse, or drug abuse within the past 24 months * History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness. * History of treatment for any gastrointestinal disorder within the past five (5) years. * History of, or presence of, asthma * History of peripheral vascular disease * History of heart failure * History of pre-existing cardiac arrythmias associated with tachycardia * History of severe sensitivity to allergens, requiring urgent medical treatment. * Females who are pregnant or lactating * History of hypersensitivity to carvedilol, or any beta adrenergic blocking drug. * Conditions upon screening which might contraindicate or require that caution be used in the administration of carvedilol, including: * sitting systolic blood pressure below 100 mmHg, or diastolic pressure below 60 mmHg. * Heart rate less than 60 beats per minute after a 5-minute rest in a seated position. * Inability to read and/or sign the consent form. * Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study. * Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums,etc.) Ninety (90) days abstinence is required. * subjects who have donated blood within four (4) weeks prior to the initial dosing for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration - Carvedilol in Plasma | Blood samples collected over 60 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Carvedilol in Plasma | Blood samples collected over 60 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) - Carvedilol in Plasma | Blood samples collected over 60 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carvedilol (Test) First Carvedilol 25 mg Tablet (test) dosed in first period followed by Coreg® 25 mg Tablet (reference) dosed in second period | 18 |
| Coreg® (Reference) First Coreg® 25 mg Tablet (reference) dosed in first period followed by Carvedilol 25 mg Tablet (test) dosed in second period | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Adverse Event | 1 | 0 |
| Washout: 7 Days | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Coreg® (Reference) First | Total | Carvedilol (Test) First |
|---|---|---|---|
| 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 | 18 Participants | 36 Participants | 18 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 13 Participants | 29 Participants | 16 Participants |
| Region of Enrollment United States | 18 participants | 36 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Male | 12 Participants | 20 Participants | 8 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Carvedilol in Plasma
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 60 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Carvedilol in Plasma | 465.29 ng*h/mL | Standard Deviation 304 |
| Coreg® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Carvedilol in Plasma | 468.81 ng*h/mL | Standard Deviation 282.83 |
90% CI: [90.34, 102.59]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Carvedilol in Plasma
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 60 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Carvedilol in Plasma | 454.24 ng*h/mL | Standard Deviation 303.44 |
| Coreg® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Carvedilol in Plasma | 456.05 ng*h/mL | Standard Deviation 279.95 |
90% CI: [90.2, 102.93]
Primary
Cmax - Maximum Observed Concentration - Carvedilol in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 60 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carvedilol | Cmax - Maximum Observed Concentration - Carvedilol in Plasma | 104.98 ng/mL | Standard Deviation 57.81 |
| Coreg® | Cmax - Maximum Observed Concentration - Carvedilol in Plasma | 107.47 ng/mL | Standard Deviation 57.95 |
90% CI: [85.69, 105.67]