Carvedilol 25 mg in 36 Fasted, Healthy, Adult Subjects
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
Criteria for Evaluation: FDA Bioequivalence Criteria
Statistical Methods: FDA bioequivalence statistical methods
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Carvedilol Carvedilol 25 mg Tablet (test) dosed in first period followed by Coreg® 25 mg Tablet (reference) dosed in second period |
Drug: Carvedilol 25 mg tablets
1 x 25 mg
|
Active Comparator: Coreg® Coreg® 25 mg Tablet (reference) dosed in first period followed by Carvedilol 25 mg Tablet (test) dosed in second period |
Drug: COREG® 25 mg tablets
1 x 25 mg
|
Outcome Measures
Primary Outcome Measures
- 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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Gateway Medical Research, Inc. | St. Charles | Missouri | United States | 63301 |
Sponsors and Collaborators
- Teva Pharmaceuticals USA
Investigators
- Principal Investigator: M David Ayra, M.D., Cetero Research, San Antonio
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 01268
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Carvedilol (Test) First | Coreg® (Reference) First |
---|---|---|
Arm/Group Description | Carvedilol 25 mg Tablet (test) dosed in first period followed by Coreg® 25 mg Tablet (reference) dosed in second period | Coreg® 25 mg Tablet (reference) dosed in first period followed by Carvedilol 25 mg Tablet (test) dosed in second period |
Period Title: First Intervention | ||
STARTED | 18 | 18 |
COMPLETED | 18 | 18 |
NOT COMPLETED | 0 | 0 |
Period Title: First Intervention | ||
STARTED | 18 | 18 |
COMPLETED | 18 | 17 |
NOT COMPLETED | 0 | 1 |
Period Title: First Intervention | ||
STARTED | 18 | 17 |
COMPLETED | 17 | 17 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Carvedilol (Test) First | Coreg® (Reference) First | Total |
---|---|---|---|
Arm/Group Description | Carvedilol 25 mg Tablet (test) dosed in first period followed by Coreg® 25 mg Tablet (reference) dosed in second period | Coreg® 25 mg Tablet (reference) dosed in first period followed by Carvedilol 25 mg Tablet (test) dosed in second period | Total of all reporting groups |
Overall Participants | 18 | 18 | 36 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
18
100%
|
18
100%
|
36
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | |||
Female |
10
55.6%
|
6
33.3%
|
16
44.4%
|
Male |
8
44.4%
|
12
66.7%
|
20
55.6%
|
Race/Ethnicity, Customized (Number) [Number] | |||
Caucasian |
16
88.9%
|
13
72.2%
|
29
80.6%
|
Black |
1
5.6%
|
5
27.8%
|
6
16.7%
|
Asian |
1
5.6%
|
0
0%
|
1
2.8%
|
Region of Enrollment (participants) [Number] | |||
United States |
18
100%
|
18
100%
|
36
100%
|
Outcome Measures
Title | Cmax - Maximum Observed Concentration - Carvedilol in Plasma |
---|---|
Description | Bioequivalence based on Cmax |
Time Frame | Blood samples collected over 60 hour period |
Outcome Measure Data
Analysis Population Description |
---|
Data from all subjects who completed the study were included in the statistical analysis. |
Arm/Group Title | Carvedilol | Coreg® |
---|---|---|
Arm/Group Description | Carvedilol 25 mg Tablet (test) dosed in either period | Coreg® 25 mg Tablet (reference) dosed in either period |
Measure Participants | 34 | 34 |
Mean (Standard Deviation) [ng/mL] |
104.98
(57.81)
|
107.47
(57.95)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Carvedilol, Coreg® |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Using GLM procedures in SAS, analysis of variance (ANOVA)was performed on log-transformed AUC0-t, AUC0-inf and Cmax at the significance level of 0.05. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Test/Ref Ratio of LS Means x 100 |
Estimated Value | 95.16 | |
Confidence Interval |
() 90% 85.69 to 105.67 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
Title | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Carvedilol in Plasma |
---|---|
Description | Bioequivalence based on AUC0-inf |
Time Frame | Blood samples collected over 60 hour period |
Outcome Measure Data
Analysis Population Description |
---|
Data from all subjects who completed the study were included in the statistical analysis. |
Arm/Group Title | Carvedilol | Coreg® |
---|---|---|
Arm/Group Description | Carvedilol 25 mg Tablet (test) dosed in either period | Coreg® 25 mg Tablet (reference) dosed in either period |
Measure Participants | 34 | 34 |
Mean (Standard Deviation) [ng*h/mL] |
465.29
(304.00)
|
468.81
(282.83)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Carvedilol, Coreg® |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Using GLM procedures in SAS, analysis of variance (ANOVA)was performed on log-transformed AUC0-t, AUC0-inf and Cmax at the significance level of 0.05. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Test/Ref Ratio of LS Means x 100 |
Estimated Value | 96.27 | |
Confidence Interval |
() 90% 90.34 to 102.59 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
Title | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Carvedilol in Plasma |
---|---|
Description | Bioequivalence based on AUC0-t |
Time Frame | Blood samples collected over 60 hour period |
Outcome Measure Data
Analysis Population Description |
---|
Data from all subjects who completed the study were included in the statistical analysis. |
Arm/Group Title | Carvedilol | Coreg® |
---|---|---|
Arm/Group Description | Carvedilol 25 mg Tablet (test) dosed in either period | Coreg® 25 mg Tablet (reference) dosed in either period |
Measure Participants | 34 | 34 |
Mean (Standard Deviation) [ng*h/mL] |
454.24
(303.44)
|
456.05
(279.95)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Carvedilol, Coreg® |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Using GLM procedures in SAS, analysis of variance (ANOVA)was performed on log-transformed AUC0-t, AUC0-inf and Cmax at the significance level of 0.05. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Test/Ref Ratio of LS Means x 100 |
Estimated Value | 96.36 | |
Confidence Interval |
() 90% 90.20 to 102.93 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
Adverse Events
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Principal Investigator is not permitted to discuss or publish trial results.
Results Point of Contact
Name/Title | Manager, Biopharmaceutics |
---|---|
Organization | Teva Pharmaceuticals USA |
Phone | 1-866-384-5525 |
clinicaltrialqueries@tevausa.com |
- 01268