Venlafaxine Hydrochloride 150 mg Extended-Release Capsules Under Fed Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01282801
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 18.3

Study Details

Study Description

Brief Summary

The objective of this study was to compare the rate and extent of absorption of venlafaxine hydrochloride 150 mg extended-release capsules (test) versus Effexor® XR (reference) administered as 1 x 150 mg extended-release capsule under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Venlafaxine Hydrochloride; Drug: Effexor® XR	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: Randomized, 2-way Crossover, Bioequivalence Study of Venlafaxine Hydrochloride 150 mg Extended-Release Capsules and Effexor® XR 150 mg Extended-Release Capsules Administered as 1 x 150 mg Extended-Release Capsules in Healthy Subjects Under Fed Conditions.
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Oct 1, 2002
• Actual Study Completion Date: Oct 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Test Product Venlafaxine Hydrochloride 150 mg Extended-Release Capsules	Drug: Venlafaxine Hydrochloride; 150 mg Extended-Release Capsule
Active Comparator: Reference Listed Drug Effexor® XR 150 mg Extended-Release Capsules	Drug: Effexor® XR; 150 mg Extended-Release Capsule; Other Names: Venlafaxine Hydrochloride (generic name)

Outcome Measures

Primary Outcome Measures

1. Cmax of Venlafaxine. [Blood samples collected over a 36 hour period.]

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

2. AUC0-t of Venlafaxine. [Blood samples collected over a 36 hour period.]

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

3. AUC0-inf of Venlafaxine. [Blood samples collected over a 36 hour period.]

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

Secondary Outcome Measures

1. Cmax of O-Desmethylvenlafaxine. [Blood samples collected over a 36 hour period.]

   Informational comparison of Cmax values for the metabolite O-Desmethylvenlafaxine.

2. AUC0-t of O-Desmethylvenlafaxine. [Blood samples collected over a 36 hour period.]

   Informational comparison of AUC0-t values for the metabolite O-Desmethylvenlafaxine.

3. AUC0-inf of O-Desmethylvenlafaxine. [Blood samples collected over a 36 hour period.]

   Informational comparison of AUC0-inf values for the metabolite O-Desmethylvenlafaxine.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Members of the community at large.

• Subjects will be females and/or males, non-smokers, 18 years of age and older.

• Female subjects will be post-menopausal or surgically sterilized.

Exclusion Criteria:

• Clinically significant illnesses within 4 weeks of the administration of study medication.

• Clinically significant surgery within 4 weeks prior to the administration of the study medication.

• Any clinically significant abnormality found during medical screening.

• Any history or presence of significant neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease.

• History or presence of any clinically significant gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug.

• Subjects with raised intra-ocular pressure or at risk of acute narrow angle glaucoma.

• Subjects predisposed to bleeding of the skin and mucous membrane.

• Subjects with a history of seizures.

• Any reason which, in the opinion of the medical sub-investigator, would prevent the subject from participating in the study.

• Abnormal laboratory tests judged clinically significant.

• Positive urine drug screen at screening.

• Positive testing for hepatitis B, hepatitis C, or HIV at screening.

• ECG abnormalities (clinically significant) or vital sign abnormalities at screening.

• Subjects with BMI > 30.0.

• History of significant alcohol abuse within six months of screening visit or any indication of the regular use of more than fourteen units of alcohol per week (1 unit equals 150 mL of wine, 360 mL of beer, or 45 mL of alcohol 45%).

• History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (cocaine, PCP, crack) within 1 year of the screening visit.

• Any food allergy, intolerance, restriction, or special diet that, in the opinion of the medical sub-investigator, contraindicates the subject's participation in the study.

• History of allergic reactions to venlafaxine hydrochloride.

• History of allergic reactions to heparin.

• Use of any drugs know to induce or inhibit hepatic drug metabolism, use of an investigational drug, or participation in an investigational study within 30 days prior to administration of the study medication.

• Use of prescription medication within 14 days prior to administration of the study medication or over-the-counter products within 7 days prior to the administration of study medication, except for topical products without systemic absorption.

• Subjects who have had a depot injection or an implant of any drug 3 months prior to administration of the study medication.

• Donation of plasma (500 mL) within 7 days of Period I dosing. Donation or loss of whole blood prior to administration of the study medication as follows:

• less than 300 mL of whole blood within 30 days or

• 300 mL to 500 mL of whole blood within 45 days or

• more than 500 mL of whole blood within 56 days.

• Positive alcohol breath test at screening.

• Subjects who have used tobacco in any form within the 90 days preceding study drug administration.

• Subjects who have consumed food or beverages containing grapefruit within 7 days prior to administration of the study medication.

• Intolerance to venipunctures.

• Additional exclusion criteria for females only:

• Breastfeeding subjects.

• Positive urine pregnancy test at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anapharm Inc.	Sainte-Foy	Quebec	Canada	G1V 2K8

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Benoit Girard, M.D., Anapharm

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01282801
• Other Study ID Numbers: 02205
• First Posted: Jan 25, 2011
• Last Update Posted: Mar 8, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Malnutrition; Venlafaxine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Velafaxine Hydrochloride (Test) First	Effexor® XR (Reference) First
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in first period followed by 150 mg Effexor® XR Capsules reference product dosed in the second period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in first period followed by 150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in the second period.
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	9	9
COMPLETED	9	8
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Velafaxine Hydrochloride (Test) First	Effexor® XR (Reference) First	Total
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in first period followed by 150 mg Effexor® XR Capsules reference product dosed in the second period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in first period followed by 150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in the second period.	Total of all reporting groups
Overall Participants	9	9	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 100%	9 100%	18 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 44.4%	1 11.1%	5 27.8%
Male	5 55.6%	8 88.9%	13 72.2%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	9 100%	9 100%	18 100%
Region of Enrollment (participants) [Number]
Canada	9 100%	9 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Cmax of Venlafaxine.
Description	Bioequivalence based on Venlafaxine Cmax (maximum observed concentration of drug substance in plasma).
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng/mL]	81.84 (37.59)	93.50 (37.73)

2. Primary Outcome

Title	AUC0-t of Venlafaxine.
Description	Bioequivalence based on Venlafaxine AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng*h/mL]	1358.37 (766.51)	1383.57 (769.22)

3. Primary Outcome

Title	AUC0-inf of Venlafaxine.
Description	Bioequivalence based on Venlafaxine AUC0-inf (area under the concentration-time curve from time zero to infinity).
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng*h/mL]	1596.83 (902.89)	1605.29 (910.77)

4. Secondary Outcome

Title	Cmax of O-Desmethylvenlafaxine.
Description	Informational comparison of Cmax values for the metabolite O-Desmethylvenlafaxine.
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng/mL]	227.02 (48.08)	236.21 (57.37)

5. Secondary Outcome

Title	AUC0-t of O-Desmethylvenlafaxine.
Description	Informational comparison of AUC0-t values for the metabolite O-Desmethylvenlafaxine.
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng*h/mL]	5591.56 (1412.83)	5748.06 (1578.70)

6. Secondary Outcome

Title	AUC0-inf of O-Desmethylvenlafaxine.
Description	Informational comparison of AUC0-inf values for the metabolite O-Desmethylvenlafaxine.
Time Frame	Blood samples collected over a 36 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Velafaxine Hydrochloride (Test)	Effexor® XR (Reference)
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in either period.	150 mg Effexor® XR Extended-Release Capsules reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng*h/mL]	7945.58 (2636.77)	8102.12 (2769.50)

Adverse Events

Time Frame	Adverse event data was collected over the course of the study, which was approximately 2 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	Velafaxine Hydrochloride (Test) First		Effexor® XR (Reference) First
Arm/Group Description	150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in first period followed by 150 mg Effexor® XR Capsules reference product dosed in the second period.		150 mg Effexor® XR Extended-Release Capsules reference product dosed in first period followed by 150 mg Venlafaxine Hydrochloride Extended-Release Capsules test product dosed in the second period.
All Cause Mortality
	Velafaxine Hydrochloride (Test) First		Effexor® XR (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Velafaxine Hydrochloride (Test) First		Effexor® XR (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Velafaxine Hydrochloride (Test) First		Effexor® XR (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/18 (66.7%)		14/18 (77.8%)
General disorders
Sore Throat	1/18 (5.6%)	1	0/18 (0%)	0
Runny Nose	1/18 (5.6%)	1	0/18 (0%)	0
Nausea	4/18 (22.2%)	4	8/18 (44.4%)	9
Drowsiness	1/18 (5.6%)	1	3/18 (16.7%)	3
Vomiting	0/18 (0%)	0	1/18 (5.6%)	1
High Blood Pressure	5/18 (27.8%)	6	4/18 (22.2%)	4
Loose Stools	1/18 (5.6%)	1	1/18 (5.6%)	1
Dizziness	1/18 (5.6%)	1	1/18 (5.6%)	1
Difficulty Swallowing	0/18 (0%)	0	1/18 (5.6%)	1
Tremors	0/18 (0%)	0	1/18 (5.6%)	1
Redness of Arm	1/18 (5.6%)	1	0/18 (0%)	0
Pain at Catheter Site	1/18 (5.6%)	1	0/18 (0%)	0
Hot Flushes	1/18 (5.6%)	1	0/18 (0%)	0
Swelling of Hand	1/18 (5.6%)	1	0/18 (0%)	0
Swollen Arm	1/18 (5.6%)	1	0/18 (0%)	0
Headache	1/18 (5.6%)	1	1/18 (5.6%)	1
Bruising of Hand	1/18 (5.6%)	1	0/18 (0%)	0
Leukocytes in Urine	0/18 (0%)	0	1/18 (5.6%)	1
Flatulence	1/18 (5.6%)	1	1/18 (5.6%)	1
Difficulty Sleeping	0/18 (0%)	0	1/18 (5.6%)	1
Back Pain	0/18 (0%)	0	1/18 (5.6%)	1
Delayed Ejaculation	1/18 (5.6%)	1	1/18 (5.6%)	1
Protein in Urine	0/18 (0%)	0	1/18 (5.6%)	1

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.