Carvedilol (25 mg) in 24 Fed, Healthy, Adult Subjects

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834873
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2

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 24 adult individuals under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Carvedilol 25 mg tablets; Drug: COREG® 25 mg tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Randomized, Two-Way Crossover, Single-Dose, Open Label Study to Evaluate the Relative Bioavailability of a Test Tablet Formulation of Carvedilol (25 mg), Compared to an Equivalent Dose of COREG® (SmithKline Beecham Pharmaceuticals) in 24 Fed, Healthy, Adult Subjects
• Study Start Date: Dec 1, 2001
• Actual Primary Completion Date: Dec 1, 2001
• Actual Study Completion Date: Dec 1, 2001

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

1. Cmax - Maximum Observed Concentration - Carvedilol in Plasma [Blood samples collected over 60 hour period]

   Bioequivalence based on Cmax

2. 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

3. 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

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

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., Gateway

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834873
• Other Study ID Numbers: 01269
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Carvedilol

Study Results

Participant Flow

Arm/Group Title	Carvedilol (Test) First	Coreg® (Reference) First
Arm/Group Description	Carvedilol 25 mg Tablet (test) dosed in first period follwed 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	12	12
COMPLETED	12	11
NOT COMPLETED	0	1
Period Title: First Intervention
STARTED	12	11
COMPLETED	12	11
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	11
COMPLETED	12	11
NOT COMPLETED	0	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 follwed 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	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 41.7%	5 41.7%	10 41.7%
Male	7 58.3%	7 58.3%	14 58.3%
Race/Ethnicity, Customized (Number) [Number]
Caucasion	11 91.7%	9 75%	20 83.3%
Black	1 8.3%	3 25%	4 16.7%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

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	23	23
Mean (Standard Deviation) [ng/mL]	89.91 (40.86)	97.05 (49.61)

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	94.77
	Confidence Interval	() 90%; 85.04 to 105.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

2. Primary Outcome

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	23	23
Mean (Standard Deviation) [ng*h/mL]	467.57 (287.12)	490.16 (337.58)

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	96.23
	Confidence Interval	() 90%; 90.59 to 102.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

3. Primary Outcome

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	23	23
Mean (Standard Deviation) [ng*h/mL]	455.91 (284.99)	478.61 (336.07)

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	96.11
	Confidence Interval	() 90%; 90.45 to 102.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

Adverse Events

Limitations/Caveats

[Not Specified]

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.