Moexipril HCl/Hydrochlorothiazide 15/25 mg Tablets Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834067
• Collaborator: (none)
• Enrollment: 60
• Locations: 2
• Arms: 2
• Duration (Months): 1
• Patients Per Site: 30
• Patients Per Site Per Month: 29.5

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of moexipril HCl/ hydrochlorothiazide 15/25 mg tablets (manufactured and distributed by TEVA Pharmaceuticals USA) with that of UNIRETIC® 15/25 mg tablets (Schwartz Pharma) in healthy, adult, non-smoking subjects under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Moexipril HCl/hydrochlorothiazide 15/25 mg tablets; Drug: UNIRETIC® 15/25 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: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of Moexipril HCl/Hydrochlorothiazide 15/25 mg Tablets Under Non-Fasting Conditions
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Nov 1, 2003
• Actual Study Completion Date: Nov 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Moexipril HCl/hydrochlorothiazide 15/25 mg tablets; 1 x 15/25 mg
Active Comparator: 2	Drug: UNIRETIC® 15/25 mg tablets; 1 x 15/25 mg

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on Cmax.

2. AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on AUC0-t.

3. AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on AUC0-inf.

4. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on Cmax.

5. AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on AUC0-t.

6. AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide. [Blood samples collected over a 192 hour period.]

   Bioequivalence based on AUC0-inf.

Secondary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat. [Blood samples collected over a 192 hour period.]

   Informational comparison of Cmax values for the metabolite Moexiprilat.

2. AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat. [Blood samples collected over a 192 hour period.]

   Informational comparison of AUC0-t values for the metabolite Moexiprilat.

3. AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat. [Blood samples collected over a 192 hour period.]

   Informational comparison of AUC0-inf values for the metabolite Moexiprilat.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All subjects selected for this study will be non-smokers at least 18 years of age.

• Subjects will have a BMI index (body mass index) of 30 or less.

Exclusion Criteria:

• Subjects with a history of chronic alcohol consumption (during past 2 years), drug addiction, or serious gastrointestinal, renal, hepatic, tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for this study.

• Subjects whose clinical laboratory test values are greater than 20% outside the normal range may be retested. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result not to be significant.

• Subjects who have a history of allergic responses to the class of drug being tested should be excluded from the study.

• All subjects will have urine samples assayed for the presence of abuse as part of the clinical laboratory screening procedures and ath check-in each study period. Subjects found to have urine concentrations of any of the tested drug will not be allowed to participate.

• Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study.

• Subjects who have taken an investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate.

• Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of child bearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Subjects who have used implanted or injected hormonal contraceptives anytime during the 180 days prior to study dosing or oral hormonal contraceptives with in 14 days of dosing will not be allowed to participate.

• All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study.

• Subjects who use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required.

• Subjects who do not tolerate venipuncture will not be allowed to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research, Inc.	St. Charles	Missouri	United States	63301
2	Bioassay Laboratory, Inc.	Houston	Texas	United States	77099

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Irwin Plisco, M.D., Gateway Medical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834067
• Other Study ID Numbers: B036544
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Test (Moexipril HCl/HCTZ) First	Reference (Uniretic®) First
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in first period followed by 15/25 mg Uniretic® Tablets reference product dosed in the second period.	15/25 mg Uniretic® Tablets reference product dosed in first period followed by 15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	30	30
COMPLETED	30	30
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	30	30
COMPLETED	30	29
NOT COMPLETED	0	1
Period Title: First Intervention
STARTED	30	29
COMPLETED	30	29
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test (Moexipril HCl/HCTZ) First	Reference (Uniretic®) First	Total
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in first period followed by 15/25 mg Uniretic® Tablets reference product dosed in the second period.	15/25 mg Uniretic® Tablets reference product dosed in first period followed by 15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 100%	30 100%	60 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 43.3%	14 46.7%	27 45%
Male	17 56.7%	16 53.3%	33 55%
Race/Ethnicity, Customized (participants) [Number]
Asian	0 0%	1 3.3%	1 1.7%
Black	7 23.3%	2 6.7%	9 15%
White	22 73.3%	25 83.3%	47 78.3%
Hispanic	1 3.3%	1 3.3%	2 3.3%
Unknown	0 0%	1 3.3%	1 1.7%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexipril.
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng/mL]	14.487 (6.706)	14.885 (6.018)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	96.7
	Confidence Interval	() 90%; 90.1 to 104
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexipril.
Description	Bioequivalence based on AUC0-t.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	35.412 (41.756)	34.917 (47.077)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	104
	Confidence Interval	() 90%; 99.9 to 108
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

3. Primary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexipril.
Description	Bioequivalence based on AUC0-inf.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	36.651 (43.262)	35.74 (47.957)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	103
	Confidence Interval	() 90%; 99.7 to 107
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

4. Primary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Hydrochlorothiazide.
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng/mL]	150.225 (42.664)	148.39 (39.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	101
	Confidence Interval	() 90%; 96 to 106
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

5. Primary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Hydrochlorothiazide.
Description	Bioequivalence based on AUC0-t.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	1105.63 (260.669)	1100.5 (271.834)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	101
	Confidence Interval	() 90%; 99.1 to 102
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

6. Primary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Hydrochlorothiazide.
Description	Bioequivalence based on AUC0-inf.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	1115.905 (259.765)	1108.329 (271.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	101
	Confidence Interval	() 90%; 99.4 to 103
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

7. Secondary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma) of Moexiprilat.
Description	Informational comparison of Cmax values for the metabolite Moexiprilat.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng/mL]	5.512 (3.241)	5.13 (2.788)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	107
	Confidence Interval	() 90%; 99.8 to 114
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

8. Secondary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) of Moexiprilat.
Description	Informational comparison of AUC0-t values for the metabolite Moexiprilat.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	215.654 (61.545)	214.286 (69.726)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	102
	Confidence Interval	() 90%; 99 to 106
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

9. Secondary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) of Moexiprilat.
Description	Informational comparison of AUC0-inf values for the metabolite Moexiprilat.
Time Frame	Blood samples collected over a 192 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Test (Moexipril HCl/HCTZ)	Reference (Uniretic®)
Arm/Group Description	15/25 mg Moexipril HCl/Hydrochlorothiazide Tablets test product dosed in either period.	15/25 mg Uniretic® Tablets reference product dosed in either period.
Measure Participants	59	59
Mean (Standard Deviation) [ng*h/mL]	376.814 (144.282)	379.994 (184.852)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Moexipril HCl/HCTZ), Reference (Uniretic®)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	103
	Confidence Interval	() 90%; 98.1 to 108
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Principal Investigator is not permitted to discuss or publish trial results.