Zolpidem Tartrate 10 mg Tablets Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00833937
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arms: 2
• Patients Per Site: 12

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of Zolpidem tartrate 10 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of AMBIEN® tablets(G.D. Searle & Co.) in healthy, adult, non-smoking subjects under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Zolpidem 10 mg tablets; Drug: AMBIEN® 10 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)
• Primary Purpose: Other
• Official Title: A Relative Bioavailability Study of Zolpidem Tartrate 10 mg Tablets Under Non-Fasting Conditions
• Study Start Date: Mar 1, 2002
• Actual Primary Completion Date: Mar 1, 2002
• Actual Study Completion Date: Mar 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zolpidem Zolpidem Tartrate 10 mg Tablet (test) dosed in first period followed by Ambien® 10 mg Tablet (reference) dosed in second period	Drug: Zolpidem 10 mg tablets; 1 x 10 mg
Active Comparator: Ambien® Ambien® 10 mg Tablet (reference) dosed in first period followed by Zolpidem Tartrate 10 mg Tablet (test) dosed in second period	Drug: AMBIEN® 10 mg tablets; 1 x 10 mg

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 24 hour period]

   Bioequivalence based on Cmax

2. AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) [Blood samples collected over 24 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) [Blood samples collected over 24 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:

• All subjects selected for this study will be non-smokers at least 18 years of age. Subjects will have a BMI (body mass index) of 30 or less.

Exclusion Criteria:

• Subjects with a significant recent history of chronic alcohol consumption, drug addiction, or serious gastrointestinal, renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, 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 to not be significant.

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novum Pharmaceutical Research Services	Pittsburgh	Pennsylvania	United States	15206
2	Bioassay Laboratory, Inc.	Houston	Texas	United States	77099

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Shirley Ann Kennedy, M.D., Novum Pharmaceuticals Research Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00833937
• Other Study ID Numbers: B016540
• First Posted: Feb 2, 2009
• Last Update Posted: Oct 8, 2020
• Last Verified: Jul 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Zolpidem (Test) First	Ambien® (Reference) First
Arm/Group Description	Zolpidem Tartrate 10 mg Tablet (test) dosed in first period followed by Ambien® 10 mg Tablet (reference) dosed in second period	Ambien® 10 mg Tablet (reference) dosed in first period followed by Zolpidem Tartrate 10 mg Tablet (test) dosed in second period
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	12
COMPLETED	11	12
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Zolpidem (Test) First	Ambien® (Reference) First	Total
Arm/Group Description	Zolpidem Tartrate 10 mg Tablet (test) dosed in first period followed by Ambien® 10 mg Tablet (reference) dosed in second period	Ambien® 10 mg Tablet (reference) dosed in first period followed by Zolpidem Tartrate 10 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	1 8.3%	2 16.7%	3 12.5%
Male	11 91.7%	10 83.3%	21 87.5%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	9 75%	7 58.3%	16 66.7%
Black	2 16.7%	4 33.3%	6 25%
Hispanic	1 8.3%	1 8.3%	2 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 24 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	Zolpidem	Ambien®
Arm/Group Description	Zolpidem Tartrate 10 mg Tablet (test) dosed in either period	Ambien® 10 mg Tablet (reference) dosed in either period
Measure Participants	23	23
Mean (Standard Deviation) [ng/mL]	117.313 (42.878)	116.452 (40.419)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem, Ambien®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	99.7
	Confidence Interval	() 90%; 93.9 to 106
	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)
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 24 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	Zolpidem	Ambien®
Arm/Group Description	Zolpidem Tartrate 10 mg Tablet (test) dosed in either period	Ambien® 10 mg Tablet (reference) dosed in either period
Measure Participants	23	23
Mean (Standard Deviation) [ng*h/mL]	541.580 (279.254)	543.732 (273.918)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem, Ambien®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	97.8
	Confidence Interval	() 90%; 92.6 to 103
	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)
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 24 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	Zolpidem	Ambien®
Arm/Group Description	Zolpidem Tartrate 10 mg Tablet (test) dosed in either period	Ambien® 10 mg Tablet (reference) dosed in either period
Measure Participants	23	23
Mean (Standard Deviation) [ng*h/mL]	530.272 (271.461)	531.866 (265.350)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem, Ambien®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	97.9
	Confidence Interval	() 90%; 92.7 to 103
	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.