Trial Outcomes & Findings for Study Evaluating the Pharmacokinetics of Venlafaxine Extended-Release (ER) and Desvenlafaxine Succinate Sustained-Release (DVS SR) 50 mg in Healthy Subjects (NCT NCT00727064)

NCT ID: NCT00727064

Last Updated: 2010-06-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

single dose

Results posted on

2010-06-02

Participant Flow

Participants were recruited in the United States from June 2008 to August 2008.

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.

Participant milestones

Participant milestones
Measure	Sequence Group A 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.	Sequence Group B 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.
Overall Study STARTED	7	7
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence Group A n=7 Participants 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.	Sequence Group B n=7 Participants 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 n=14 Participants Total of all reporting groups
Age Continuous	30.14 years STANDARD_DEVIATION 10.37 • n=5 Participants	28.29 years STANDARD_DEVIATION 8.90 • n=7 Participants	29.21 years STANDARD_DEVIATION 9.33 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Maximum Concentration (Cmax) of Venlafaxine After Single Dose of Venlafaxine Extended-release (VEN ER) by Metabolizer Status	26.16 ng/mL (90% CI) 90% Confidence Interval 17.70 • Interval 20.01 to 34.19	77.46 ng/mL (90% CI) 90% Confidence Interval 32.36 • Interval 59.25 to 101.25

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Area Under the Concentration-time Curve (AUC) of Venlafaxine After Single Dose of VEN ER by Metabolizer Status	389.68 ng*h/mL (90% CI) 90% Confidence Interval 462.45 • Interval 247.02 to 614.72	2328.41 ng*h/mL (90% CI) 90% Confidence Interval 3460.47 • Interval 1475.99 to 3673.13

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status	95.63 ng/mL (90% CI) 90% Confidence Interval 27.40 • Interval 51.77 to 176.68	15.73 ng/mL (90% CI) 90% Confidence Interval 20.27 • Interval 8.51 to 29.06

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status	2703.50 ng*h/mL (90% CI) 90% Confidence Interval 540.96 • Interval 1191.9 to 6132.19	436.14 ng*h/mL (90% CI) 90% Confidence Interval 442.86 • Interval 192.28 to 989.26

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of Desvenlafaxine Succinate Sustained-Release (DVS SR) by Metabolizer Status	102.22 ng/mL (90% CI) 90% Confidence Interval 15.35 • Interval 83.52 to 125.12	125.32 ng/mL (90% CI) 90% Confidence Interval 28.34 • Interval 101.8 to 154.28

PRIMARY outcome

Timeframe: single dose

Population: All participants from sequence groups A and B who received a single dose of venlafaxine ER.

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.

Outcome measures

Outcome measures
Measure	Extensive Metabolizers (EM) n=7 Participants Identified as EM from CYP2D6 testing at screening	Poor Metabolizers (PM) n=7 Participants Identified as PM from CYP2D6 testing at screening
Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of DVS SR by Metabolizer Status	2701.79 ng*h/mL (90% CI) 90% Confidence Interval 414.79 • Interval 2024.74 to 3605.25	3111.25 ng*h/mL (90% CI) 90% Confidence Interval 1050.76 • Interval 2316.01 to 4179.55

Adverse Events

Desvenlafaxine Succinate Sustained-Release (DVS SR)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Venlafaxine Extended Release (VEN ER)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Desvenlafaxine Succinate Sustained-Release (DVS SR) n=7 participants at risk SAE or AE reported on DVS SR regardless of which arm or period of trial.	Venlafaxine Extended Release (VEN ER) n=7 participants at risk SAE or AE reported on VEN ER regardless of which arm or period of trial.
Gastrointestinal disorders Nausea	14.3% 1/7	14.3% 1/7
Nervous system disorders Headache	0.00% 0/7	28.6% 2/7
Nervous system disorders Syncope vasovagal	0.00% 0/7	14.3% 1/7
Psychiatric disorders Insomina	14.3% 1/7	0.00% 0/7

Additional Information

U. S. Contact Center

Wyeth

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER