Trandolapril 4 mg Tablet Under Non-Fasting Conditions - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Bio-equivalence Study; Intervention Model: Crossover Assignment; Masking: Open Label
Condition:	Healthy
Interventions:	Drug: Trandolapril 4 mg Tablets Drug: Mavik® 4 mg Tablets

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Trandolapril (Test) First	Trandolapril 4 mg Tablet (test) dosed in first period followed by Mavik® 4 mg Tablet (reference) dosed in second period
Mavik® (Reference) First	Mavik® 4 mg Tablet (reference) dosed in first period followed by Trandolapril 4 mg Tablet (test) dosed in second period

Participant Flow for 2 periods

Period 1: First Intervention

	Trandolapril (Test) First	Mavik® (Reference) First
STARTED	25	25
COMPLETED	25	25
NOT COMPLETED	0	0

Period 2: Second Intervention

	Trandolapril (Test) First	Mavik® (Reference) First
STARTED	25	25
COMPLETED	24	24
NOT COMPLETED	1	1
Missed 72 hour blood draw	1	1

Baseline Characteristics

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Reporting Groups

	Description
Trandolapril (Test) First	Trandolapril 4 mg Tablet (test) dosed in first period followed by Mavik® 4 mg Tablet (reference) dosed in second period
Mavik® (Reference) First	Mavik® 4 mg Tablet (reference) dosed in first period followed by Trandolapril 4 mg Tablet (test) dosed in second period
Total	Total of all reporting groups

Baseline Measures

	Trandolapril (Test) First	Mavik® (Reference) First	Total
Number of Participants [units: participants]	25	25	50
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	25	25	50
>=65 years	0	0	0
Gender [units: participants]
Female	10	11	21
Male	15	14	29
Race/Ethnicity, Customized [units: Participants]
Caucasian	17	18	35
Black	6	4	10
Asian	2	3	5
Region of Enrollment [units: participants]
Canada	25	25	50

Outcome Measures

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1. Primary:

Cmax - Maximum Observed Concentration [ Time Frame: Blood samples collected over 72 hour period ]

Measure Type	Primary
Measure Title	Cmax - Maximum Observed Concentration
Measure Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 72 hour period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.

Reporting Groups

	Description
Trandolapril	Trandolapril 4 mg Tablet (test) dosed in either period
Mavik®	Mavik® 4 mg Tablet (reference) dosed in either period

Measured Values

	Trandolapril	Mavik®
Number of Participants Analyzed [units: participants]	50	50
Cmax - Maximum Observed Concentration [units: ng/mL] Mean ± Standard Deviation	5.2604 ± 3.8238	5.4938 ± 3.7393

Statistical Analysis 1 for Cmax - Maximum Observed Concentration

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of Geometric Means ^[3]	96.00
90% Confidence Interval	( 85.13 to 108.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
[3]	Other relevant estimation information:
	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary:

AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) [ Time Frame: Blood samples collected over 72 hour period ]

Measure Type	Primary
Measure Title	AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Measure Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 72 hour period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from all subjects who completed the study were included in the statistical analysis. Not all data from completed subjects could be used to determine AUC0-inf.

Reporting Groups

	Description
Trandolapril	Trandolapril 4 mg Tablet (test) dosed in either period
Mavik®	Mavik® 4 mg Tablet (reference) dosed in either period

Measured Values

	Trandolapril	Mavik®
Number of Participants Analyzed [units: participants]	20	22
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) [units: ng*h/mL] Mean ± Standard Deviation	7.0104 ± 1.9298	7.9967 ± 2.8867

Statistical Analysis 1 for AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of Geometric Means ^[3]	103.81
90% Confidence Interval	( 96.72 to 111.41 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
[3]	Other relevant estimation information:
	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

3. Primary:

AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) [ Time Frame: Blood samples collected over 72 hour period ]

Measure Type	Primary
Measure Title	AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Measure Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 72 hour period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.

Reporting Groups

	Description
Trandolapril	Trandolapril 4 mg Tablet (test) dosed in either period
Mavik®	Mavik® 4 mg Tablet (reference) dosed in either period

Measured Values

	Trandolapril	Mavik®
Number of Participants Analyzed [units: participants]	50	50
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) [units: ng*h/mL] Mean ± Standard Deviation	6.9056 ± 2.7329	6.7143 ± 2.4740

Statistical Analysis 1 for AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of Geometric Means ^[3]	102.37
90% Confidence Interval	( 97.34 to 107.65 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
[3]	Other relevant estimation information:
	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

4. Secondary:

Cmax - Trandolaprilat [ Time Frame: Blood samples collected over 72 hour period ]

Measure Type	Secondary
Measure Title	Cmax - Trandolaprilat
Measure Description	Informational Purposes Only
Time Frame	Blood samples collected over 72 hour period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.

Reporting Groups

	Description
Trandolapril	Trandolapril 4 mg Tablet (test) dosed in either period
Mavik®	Mavik® 4 mg Tablet (reference) dosed in either period

Measured Values

	Trandolapril	Mavik®
Number of Participants Analyzed [units: participants]	50	50
Cmax - Trandolaprilat [units: ng/mL] Mean ± Standard Deviation	6.9610 ± 2.5672	6.6815 ± 2.4413

Statistical Analysis 1 for Cmax - Trandolaprilat

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of Geometric Means ^[3]	103.76
90% Confidence Interval	( 100.08 to 107.57 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
[3]	Other relevant estimation information:
	Informational Purposes Only

5. Secondary:

AUC0-72 - Trandolaprilat [ Time Frame: Blood samples collected over 72 hour period ]

Measure Type	Secondary
Measure Title	AUC0-72 - Trandolaprilat
Measure Description	Informational Purposes Only
Time Frame	Blood samples collected over 72 hour period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.

Reporting Groups

	Description
Trandolapril	Trandolapril 4 mg Tablet (test) dosed in either period
Mavik®	Mavik® 4 mg Tablet (reference) dosed in either period

Measured Values

	Trandolapril	Mavik®
Number of Participants Analyzed [units: participants]	50	50
AUC0-72 - Trandolaprilat [units: ng*h/mL] Mean ± Standard Deviation	127.6059 ± 23.9616	123.4560 ± 22.6436

Statistical Analysis 1 for AUC0-72 - Trandolaprilat

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of Least Squares Means ^[3]	103.34
90% Confidence Interval	( 100.84 to 105.92 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
[3]	Other relevant estimation information:
	Informational Purposes Only

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Principal Investigator is not permitted to discuss or publish trial results.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Manager, Biopharmaceutics
Organization: Teva Pharmaceuticals USA
phone: 1-866-384-5525
e-mail: clinicaltrialqueries@tevausa.com

No publications provided

ClinicalTrials.gov Identifier:	NCT00840073 History of Changes
Other Study ID Numbers:	2004-842
Study First Received:	February 6, 2009
Results First Received:	July 6, 2009
Last Updated:	July 6, 2009
Health Authority:	Canada: Ethics Review Committee