90 mg Fluoxetine Hydrochloride Capsules Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01247285
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 13

Study Details

Study Description

Brief Summary

This study compared the relative bioavailability (rate and extent of absorption) of 90 mg Fluoxetine Hydrochloride Capsules by Teva Pharmaceuticals, USA with that of 90 mg PROZAC WEEKLY® Capsules by Eli Lilly and Company following a single oral dose (1 x 90 mg) in healthy adult volunteers under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Fluoxetine Hydrochloride; Drug: PROZAC WEEKLY®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 90 mg Fluoxetine Hydrochloride Capsules Under Non-Fasting Conditions
• Study Start Date: May 1, 2001
• Actual Primary Completion Date: Jul 1, 2001
• Actual Study Completion Date: Jul 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Test Product 90 mg Fluoxetine Hydrochloride Capsules (Teva)	Drug: Fluoxetine Hydrochloride; 90 mg Capsules
Active Comparator: Reference Listed Drug 90 mg PROZAC WEEKLY® Capsules (Eli Lilly)	Drug: PROZAC WEEKLY®; 90 mg Capsules; Other Names: Fluoxetine Hydrochloride (generic name)

Outcome Measures

Primary Outcome Measures

1. Cmax of Fluoxetine. [Blood samples collected over a 25 day period.]

   Bioequivalence based on Fluoxetine Cmax (maximum observed concentration of drug substance in plasma).

2. AUC0-t of Fluoxetine. [Blood samples collected over a 25 day period.]

   Bioequivalence based on Fluoxetine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).

3. AUC0-inf of Fluoxetine. [Blood samples collected over a 25 day period.]

   Bioequivalence based on Fluoxetine AUC0-inf (area under the concentration-time curve from time zero to infinity).

Secondary Outcome Measures

1. Cmax of Norfluoxetine. [Blood samples collected over a 25 day period.]

   Informational comparison of Cmax values for the metabolite Norfluoxetine.

2. AUC0-t of Norfluoxetine. [Blood samples collected over a 25 day period.]

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

3. AUC0-inf of Norfluoxetine. [Blood samples collected over a 25 day period.]

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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Screening Demographics: All volunteers selected for this study will be healthy men or women 18 years or age or older at the time of dosing. The weight range will not exceed

• 15% for height and body frame as per Desirable Weights for Men - 1983 Metropolitan Height and Weight Table or as per Desirable Weights for Women - 1983 Metropolitan Height and Weight Table.

• Screening Procedures: Each volunteer will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.

• If female and:

• Of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), or

• Is postmenopausal for at least 1 year, or

• Is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion Criteria:

• Volunteers with a recent history of drug or alcohol addiction or abuse.

• Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurological system(s) or psychiatric disease (as determined by the clinical investigators).

• Volunteers whose clinical laboratory test values are outside the acceptable reference range and when confirmed on re-examination are deemed to be clinically significant.

• Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive HIV antibody screen.

• Volunteers demonstrating a positive drug abuse screen when screened for this study.

• Female volunteers demonstrating a positive pregnancy screen.

• Female volunteers who are currently breastfeeding.

• Volunteers with a history of allergic response(s) to fluoxetine or related drugs.

• Volunteers with a history of clinically significant allergies including drug allergies.

• Volunteers with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).

• Volunteers who currently use tobacco products.

• Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to Period I dosing.

• Volunteers who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate blood for 4 weeks after completing the study.

• Volunteers who have donated plasma within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for 4 weeks after completing the study.

• Volunteers who report receiving any investigational drug within 30 days prior to Period I dosing.

• Volunteers who report taking any systemic prescription medications in the 14 days prior to Period I dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd.	Fargo	North Dakota	United States	58102

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D Carlson, Pharm.D., PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01247285
• Other Study ID Numbers: R01-141
• First Posted: Nov 24, 2010
• Last Update Posted: Feb 21, 2011
• Last Verified: Jan 1, 2011

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

Study Results

Participant Flow

Arm/Group Title	Fluoxetine Hydrochloride (Test) First	Prozac® Weekly (Reference) First
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in first period followed by 90 mg Prozac® Weekly Capsules reference product dosed in the second period.	90 mg Prozac® Weekly Capsules reference product dosed in first period followed by 90 mg Fluoxetine Hydrochloride Capsules test product dosed in the second period.
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluoxetine Hydrochloride (Test) First	Prozac® Weekly (Reference) First	Total
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in first period followed by 90 mg Prozac® Weekly Capsules reference product dosed in the second period.	90 mg Prozac® Weekly Capsules reference product dosed in first period followed by 90 mg Fluoxetine Hydrochloride Capsules test product dosed in the second period.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 46.2%	4 30.8%	10 38.5%
Male	7 53.8%	9 69.2%	16 61.5%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	13 100%	13 100%	26 100%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Cmax of Fluoxetine.
Description	Bioequivalence based on Fluoxetine Cmax (maximum observed concentration of drug substance in plasma).
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng/mL]	75.32 (14.7)	69.86 (14.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	107.81
	Confidence Interval	(2-Sided) 90%; 97.37 to 119.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t of Fluoxetine.
Description	Bioequivalence based on Fluoxetine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	4148.71 (719.0)	4120.11 (614.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	100.69
	Confidence Interval	(2-Sided) 90%; 92.90 to 109.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.

3. Primary Outcome

Title	AUC0-inf of Fluoxetine.
Description	Bioequivalence based on Fluoxetine AUC0-inf (area under the concentration-time curve from time zero to infinity).
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	4432.21 (1591.0)	4398.46 (1277.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	100.77
	Confidence Interval	(2-Sided) 90%; 93.53 to 108.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.

4. Secondary Outcome

Title	Cmax of Norfluoxetine.
Description	Informational comparison of Cmax values for the metabolite Norfluoxetine.
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng/mL]	35.11 (12.6)	33.47 (13.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	104.88
	Confidence Interval	(2-Sided) 90%; 98.53 to 111.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

5. Secondary Outcome

Title	AUC0-t of Norfluoxetine.
Description	Informational comparison of AUC0-t values for the metabolite Norfluoxetine.
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	114575.21 (3451)	10849.08 (2978)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	105.64
	Confidence Interval	(2-Sided) 90%; 99.97 to 111.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

6. Secondary Outcome

Title	AUC0-inf of Norfluoxetine.
Description	Informational comparison of AUC0-inf values for the metabolite Norfluoxetine.
Time Frame	Blood samples collected over a 25 day period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Fluoxetine Hydrochloride (Test)	Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.	90 mg Prozac® Weekly Capsules reference product dosed in first either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	13505.84 (5234)	13365.13 (6325)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine Hydrochloride (Test), Prozac® Weekly (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	101.05
	Confidence Interval	(2-Sided) 90%; 94.76 to 107.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	This analysis was for informational purposes only and was not used to establish bioequivalence.

Adverse Events

Time Frame	Adverse event data was collected over the course of the study, which was approximately 6 weeks in duration.
Adverse Event Reporting Description	Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
Arm/Group Title	Fluoxetine Hydrochloride (Test)		Prozac® Weekly (Reference)
Arm/Group Description	90 mg Fluoxetine Hydrochloride Capsules test product dosed in either period.		90 mg Prozac® Weekly Capsules reference product dosed in either period.
All Cause Mortality
	Fluoxetine Hydrochloride (Test)		Prozac® Weekly (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluoxetine Hydrochloride (Test)		Prozac® Weekly (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Fluoxetine Hydrochloride (Test)		Prozac® Weekly (Reference)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/26 (42.3%)		11/26 (42.3%)
General disorders
Headache	6/26 (23.1%)	8	6/26 (23.1%)	8
Malaise	2/26 (7.7%)	2	1/26 (3.8%)	1
Nausea	3/26 (11.5%)	4	2/26 (7.7%)	2
Pharyngitis	1/26 (3.8%)	1	4/26 (15.4%)	4

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.