FindTrial
Sign In

Study Evaluating the Effect of Desvenlafaxine on the Pharmacokinetics of Midazolam

An Open-Label, Two-Period, Sequential Drug Interaction Study to Evaluate the Effect of Multiple Doses of Desvenlafaxine Succinate Sustained Release (DVS SR) on the Pharmacokinetics of Midazolam When Coadministered in Healthy Subjects

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00952653
Enrollment
28
Registered
2009-08-06
Start date
2010-06-30
Completion date
2010-08-31
Last updated
2011-08-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Major Depressive Disorder

Keywords

depression

Brief summary

The main purpose of this study is to evaluate the effect of desvenlafaxine administered as DVS SR on the pharmacokinetics of midazolam in healthy male and female subjects. The amount of drug in the body and the effect of the drug will also be evaluated.

Interventions

DRUGDesvenlafaxine Succinate Sustained Release

50 mg DVS SR tablet days 1-6, period 2 only.

DRUGMidazolam

4 mg midazolam (2 mL midazolam syrup) day 1, period 1 and day 6, period 2.

Sponsors

Pfizer
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

* Men or non-pregnant, non-lactating women, 18 to 55 years of age inclusive at screening. * Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG). * Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 Ilbs).

Exclusion criteria

* Presence or history of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. * Presence or history of glaucoma or intraocular pressure. * Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational product. * Allergy to midazolam, other benzodiazepine, desvenlafaxine, or venlafaxine. * Acute disease state (eg, nausea, vomiting, fever, or diarrhea) with 7 days before study day 1. * Admitted alcohol abuse or history of alcohol use that may interfere with the subject's ability to comply with the protocol requirements. History of drug abuse within 1 year before study day 1.

Design outcomes

Primary

MeasureTime frameDescription
Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosingAUCinf measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL).
Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosingCmax measured as nanograms per milliliters (ng/mL).
1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing1-Hydroxy-Midazolam is an analyte of Midazolam.
1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing—

Secondary

MeasureTime frame
1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing
Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing
1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing
Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing
Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing
1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SRPeriod 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Countries

United States

Participant flow

Participants by arm

ArmCount
DVS SR 50 mg, Midazolam 4 mg
Midazolam 4 mg syrup (2 mg/mL) as a single oral dose Period 1 / Day 1. DVS SR 50 mg tablet as a single oral dose Period 2 / Day 1 to Day 5 (steady state); DVS SR 50 mg tablet as a single oral dose and midazolam 4 mg syrup (2 mg/mL) as a single oral dose Period 2 / Day 6.
28
Total28

Baseline characteristics

CharacteristicDVS SR 50 mg, Midazolam 4 mg
Age, Customized
18 to 25 years
2 participants
Age, Customized
26 to 35 years
9 participants
Age, Customized
36 to 45 years
13 participants
Age, Customized
> 45 years
4 participants
Sex: Female, Male
Female
12 Participants
Sex: Female, Male
Male
16 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
21 / 2816 / 2824 / 28
serious
Total, serious adverse events
0 / 280 / 280 / 28

Outcome results

Primary

1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR

1-Hydroxy-Midazolam is an analyte of Midazolam.

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR36.87 ng*hr/mLStandard Deviation 28.23
DVS SR 50 mg, Midazolam 4 mg (Period 2)1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR30.74 ng*hr/mLStandard Deviation 14.649
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference). Based on the sample size, this study has at least 85% power overall to demonstrate the lack of an interaction \[that is, equivalence in both AUCinf and Cmax and both midazolam and 1-hydroxy midazolam\], where overall study power is to be based on the product of the individual powers of the parameters of interest.90% CI: [87.43, 97.97]
Primary

1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR14.93 ng/mLStandard Deviation 6.5282
DVS SR 50 mg, Midazolam 4 mg (Period 2)1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR15.10 ng/mLStandard Deviation 6.2472
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference). Based on the sample size, this study has at least 85% power overall to demonstrate the lack of an interaction \[that is, equivalence in both AUCinf and Cmax and both midazolam and 1-hydroxy midazolam\], where overall study power is to be based on the product of the individual powers of the parameters of interest.90% CI: [92.96, 110.11]
Primary

Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR

AUCinf measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL).

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population: all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR54.69 ng*hr/mLStandard Deviation 26.67
DVS SR 50 mg, Midazolam 4 mg (Period 2)Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR39.45 ng*hr/mLStandard Deviation 13.301
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference). Based on the sample size, this study has at least 85% power overall to demonstrate the lack of an interaction \[that is, equivalence in both AUCinf and Cmax and both midazolam and 1-hydroxy midazolam\], where overall study power is to be based on the product of the individual powers of the parameters of interest.90% CI: [65.08, 78.33]
Primary

Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR

Cmax measured as nanograms per milliliters (ng/mL).

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR21.20 ng/mLStandard Deviation 7.1216
DVS SR 50 mg, Midazolam 4 mg (Period 2)Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR18.24 ng/mLStandard Deviation 5.1116
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference). Based on the sample size, this study has at least 85% power overall to demonstrate the lack of an interaction \[that is, equivalence in both AUCinf and Cmax and both midazolam and 1-hydroxy midazolam\], where overall study power is to be based on the product of the individual powers of the parameters of interest.90% CI: [79.04, 93.74]
Secondary

1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR37.09 ng*hr/mLStandard Deviation 25.371
DVS SR 50 mg, Midazolam 4 mg (Period 2)1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR32.42 ng*hr/mLStandard Deviation 14.881
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference)90% CI: [80.42, 94.96]
Secondary

1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (MEAN)Dispersion
Midazolam 4 mg (Period 1)1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR5.396 hrStandard Deviation 2.0638
DVS SR 50 mg, Midazolam 4 mg (Period 2)1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR4.616 hrStandard Deviation 1.7976
Secondary

1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the median.

ArmMeasureValue (MEDIAN)
Midazolam 4 mg (Period 1)1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR1.00 hr
DVS SR 50 mg, Midazolam 4 mg (Period 2)1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR0.500 hr
Secondary

Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Midazolam 4 mg (Period 1)Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR52.85 ng*hr/mLStandard Deviation 23.98
DVS SR 50 mg, Midazolam 4 mg (Period 2)Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR38.11 ng*hr/mLStandard Deviation 12.522
Comparison: DVS SR + Midazolam (test) versus Midazolam (reference)90% CI: [66.04, 78.72]
Secondary

Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the mean.

ArmMeasureValue (MEAN)Dispersion
Midazolam 4 mg (Period 1)Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR5.320 hrStandard Deviation 1.5948
DVS SR 50 mg, Midazolam 4 mg (Period 2)Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR4.648 hrStandard Deviation 1.7436
Secondary

Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Population: PK parameter analysis population; N=number of participants contributing to the median.

ArmMeasureValue (MEDIAN)
Midazolam 4 mg (Period 1)Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR0.517 hr
DVS SR 50 mg, Midazolam 4 mg (Period 2)Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR0.500 hr

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026