Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study Evaluating the Pharmacokinetics of Venlafaxine Extended-Release (ER) and Desvenlafaxine Succinate Sustained-Release (DVS SR) 50 mg in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00727064
Recruitment Status : Completed
First Posted : August 1, 2008
Results First Posted : April 19, 2010
Last Update Posted : June 2, 2010
Sponsor:
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Healthy
Interventions Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
Drug: Venlafaxine Extended Release (VEN ER)
Enrollment 14
Recruitment Details Participants were recruited in the United States from June 2008 to August 2008.
Pre-assignment Details Participants were screened for cytochrome P450 2D6 (CYP2D6) genotype to identify 7 “extensive metabolizers” and 7 “poor metabolizers” (inclusion criteria). Eligible participants were then randomly assigned to a sequence group.
Arm/Group Title Sequence Group A Sequence Group B
Hide Arm/Group Description Day 1: single 50mg oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) in a fasting state. Days 1-6: 120 hours of PK sampling. Days 7-10: Wash out period. Day 11: single 75mg oral dose of Venlafaxine ER (VEN ER) in a fasting state. Day 11-16: 120 hours of PK sampling. Day 1: single 75mg oral dose of Venlafaxine Extended Release (VEN ER) in a fasting state. Days 1-6: 120 hours of PK sampling. Days 7-10: Wash out period. Day 11: single 50mg oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) in a fasting state. Day 11-16: 120 hours of PK sampling.
Period Title: Overall Study
Started 7 7
Completed 7 7
Not Completed 0 0
Arm/Group Title Sequence Group A Sequence Group B Total
Hide Arm/Group Description Day 1: single 50mg oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) in a fasting state. Days 1-6: 120 hours of PK sampling. Days 7-10: Wash out period. Day 11: single 75mg oral dose of Venlafaxine ER (VEN ER) in a fasting state. Day 11-16: 120 hours of PK sampling. Day 1: single 75mg oral dose of Venlafaxine Extended Release (VEN ER) in a fasting state. Days 1-6: 120 hours of PK sampling. Days 7-10: Wash out period. Day 11: single 50mg oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) in a fasting state. Day 11-16: 120 hours of PK sampling. Total of all reporting groups
Overall Number of Baseline Participants 7 7 14
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 14 participants
30.14  (10.37) 28.29  (8.90) 29.21  (9.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 14 participants
Female
1
  14.3%
3
  42.9%
4
  28.6%
Male
6
  85.7%
4
  57.1%
10
  71.4%
1.Primary Outcome
Title Maximum Concentration (Cmax) of Venlafaxine After Single Dose of Venlafaxine Extended-release (VEN ER) by Metabolizer Status
Hide Description Cmax is a measure of drug metabolism and presented as least squares geometric mean with 90% Confidence Interval. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng/mL (90% CI)
26.16
(20.01 to 34.19)
77.46
(59.25 to 101.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
2.Primary Outcome
Title Area Under the Concentration-time Curve (AUC) of Venlafaxine After Single Dose of VEN ER by Metabolizer Status
Hide Description AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng*h/mL (90% CI)
389.68
(247.02 to 614.72)
2328.41
(1475.99 to 3673.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
3.Primary Outcome
Title Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status
Hide Description Cmax is a measure of drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng/mL (90% CI)
95.63
(51.77 to 176.68)
15.73
(8.51 to 29.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
4.Primary Outcome
Title Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status
Hide Description AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng*h/mL (90% CI)
2703.50
(1191.90 to 6132.19)
436.14
(192.28 to 989.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
5.Primary Outcome
Title Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of Desvenlafaxine Succinate Sustained-Release (DVS SR) by Metabolizer Status
Hide Description Cmax is a measure of drug metabolism and is presented as least squares geometric mean with 90% Confidence Interval.Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng/mL (90% CI)
102.22
(83.52 to 125.12)
125.32
(101.80 to 154.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
6.Primary Outcome
Title Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of DVS SR by Metabolizer Status
Hide Description AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.
Time Frame single dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants from sequence groups A and B who received a single dose of venlafaxine ER.
Arm/Group Title Extensive Metabolizers (EM) Poor Metabolizers (PM)
Hide Arm/Group Description:
Identified as EM from CYP2D6 testing at screening
Identified as PM from CYP2D6 testing at screening
Overall Number of Participants Analyzed 7 7
Geometric Mean (90% Confidence Interval)
Unit of Measure: ng*h/mL (90% CI)
2701.79
(2024.74 to 3605.25)
3111.25
(2316.01 to 4179.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Extensive Metabolizers (EM), Poor Metabolizers (PM)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments [Not Specified]
Method ANOVA
Comments PM compared to EM using least squares geometric means. Analysis of variance with phenotype and sequence as factors.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Desvenlafaxine Succinate Sustained-Release (DVS SR) Venlafaxine Extended Release (VEN ER)
Hide Arm/Group Description SAE or AE reported on DVS SR regardless of which arm or period of trial. SAE or AE reported on VEN ER regardless of which arm or period of trial.
All-Cause Mortality
Desvenlafaxine Succinate Sustained-Release (DVS SR) Venlafaxine Extended Release (VEN ER)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Desvenlafaxine Succinate Sustained-Release (DVS SR) Venlafaxine Extended Release (VEN ER)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   0/7 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Desvenlafaxine Succinate Sustained-Release (DVS SR) Venlafaxine Extended Release (VEN ER)
Affected / at Risk (%) Affected / at Risk (%)
Total   2   4 
Gastrointestinal disorders     
Nausea *  1/7 (14.29%)  1/7 (14.29%) 
Nervous system disorders     
Headache *  0/7 (0.00%)  2/7 (28.57%) 
Syncope vasovagal *  0/7 (0.00%)  1/7 (14.29%) 
Psychiatric disorders     
Insomina *  1/7 (14.29%)  0/7 (0.00%) 
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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 PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: U. S. Contact Center
Organization: Wyeth
EMail: clintrialresults@wyeth.com
Layout table for additonal information
Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
ClinicalTrials.gov Identifier: NCT00727064     History of Changes
Other Study ID Numbers: 3151A1-4414
First Submitted: July 29, 2008
First Posted: August 1, 2008
Results First Submitted: August 31, 2009
Results First Posted: April 19, 2010
Last Update Posted: June 2, 2010