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Open Label Drug Interaction Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) 100mg On The Pharmacokinetics Of Aripiprazole When Coadministered To Healthy Subjects

An Open-Label, 2-Period Sequential Drug Interaction Study To Evaluate The Effect Of A 100 Mg Dose Of Desvenlafaxine SR On The Pharmacokinetics Of Aripiprazole When Coadministered In Healthy Subjects

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01188668
Enrollment
38
Registered
2010-08-25
Start date
2010-08-31
Completion date
2010-10-31
Last updated
2011-11-07

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

Conditions

CYP3A4 Protein, Human, Cytochrome P-450 CYP2D6, Pharmacokinetics

Keywords

Pharmacokinetic, safety and tolerability, genetic testing, CYP 2D6 and CYP 3A4

Brief summary

The goal of this study is to evaluate the effect of multiple doses of Desvenlafaxine Sustained Release (SR) on the pharmacokinetics of Aripiprazole when coadministered to healthy adult subjects. This study will also evaluate the safety and tolerability of Desvenlafaxine SR and Aripiprazole when coadministered to healthy adult subjects.

Interventions

DRUGAripiprazole

Period 1-Aripiprazole 5mg on study day 1.

DRUGAripiprazole + desvenlafaxine succinate sustained release

Period 2-Desvenlafaxine SR 100mg on days 1-19 with coadministration of Aripiprazole 5mg on day 7.

Sponsors

Pfizer
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

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

Inclusion criteria

* Healthy male and/or female subjects between the ages of 18 and 55 years * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight \>50 kg (110 lbs) * Nonsmoker or smoker of fewer than 5 cigarettes per day as determined by history * An informed consent document signed and dated by the subject

Exclusion criteria

* History of significant blood, kidney, endocrine, lung, gastrointestinal, heart, liver, psychiatric, neurologic, or allergic disease * History of seizure disorder * Presence or history of glaucoma or increased intraocular pressure * Allergy to or unable to tolerate aripiprazole, desvenlafaxine, or venlafaxine * History of substance abuse within 1 year of study * A positive urine drug screen * Treatment with an investigational drug within 30 days * Consumption of grapefruit or grapefruit related citrus fruits * 12 lead ECG demonstrating QTc \>450 msec at screening * Pregnant or nursing females * Use of prescription or nonprescription drugs and dietary supplements * History of sensitivity to heparin or heparin induced thrombocytopenia * Severe acute or chronic medical or psychiatric condition or laboratory abnormality

Design outcomes

Primary

MeasureTime frameDescription
Aripiprazole Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞); measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL).

Secondary

MeasureTime frameDescription
Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Time for maximum observed plasma concentration.
Aripiprazole Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf); measured as milliliters per minute (mL/min).
Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Calculated as Dose / (AUCinf \* kel); where kel=terminal phase rate constant.
Dehydro-aripiprazole (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Dehydro-aripiprazole is a metabolite of Aripiprazole. Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing—
Aripiprazole Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Cmax measured as nanograms per milliliters (ng/mL).
Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Dehydro-aripiprazole (Metabolite) Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf).
Dehydro-aripiprazole (Metabolite) Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20—
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mgPeriod 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosingSummary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mgPeriod 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosingSummary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.
Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SRPeriod 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20Time for maximum observed plasma concentration.

Countries

United States

Participant flow

Participants by arm

ArmCount
Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg
Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1. DVS SR as a single oral dose of 100 mg Period 2 / Day 1 through Day 6 (steady state) and Day 7 though 19. Aripiprazole as a single oral dose of 5 mg coadministered with the DVS SR dose on Period 2 / Day 7.
38
Total38

Withdrawals & dropouts

PeriodReasonFG000
Period 1: ARIP AloneProtocol Violation2
Period 2: Coadministration ARIP + DVS SRLost to Follow-up2
Period 2: Coadministration ARIP + DVS SRWithdrawal by Subject1

Baseline characteristics

CharacteristicAripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg
Age Continuous35.2 years
STANDARD_DEVIATION 6.6
Sex: Female, Male
Female
18 Participants
Sex: Female, Male
Male
20 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
14 / 385 / 369 / 35
serious
Total, serious adverse events
0 / 380 / 360 / 35

Outcome results

Primary

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

Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞); measured as nanograms multiplied by hours divided by milliliters (ng\*hr/mL).

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

Population: Pharmacokinetic (PK) parameter analysis population: all randomized 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
Aripiprazole 5 mg (Period 1)Aripiprazole Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR1494 ng*hr/mLStandard Deviation 699.98
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR1604 ng*hr/mLStandard Deviation 561.45
Comparison: DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)90% CI: [101.39, 110.76]
Secondary

Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf); measured as milliliters per minute (mL/min).

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR55.76 mL/minStandard Deviation 25.345
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR51.92 mL/minStandard Deviation 19.655
Secondary

Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR

Calculated as Dose / (AUCinf \* kel); where kel=terminal phase rate constant.

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR397.3 litersStandard Deviation 129.28
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR368.1 litersStandard Deviation 102.01
Secondary

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

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

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Aripiprazole Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR24.66 ng/mLStandard Deviation 7.6031
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR24.69 ng/mLStandard Deviation 7.4186
Comparison: DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)90% CI: [92.94, 109.87]
Secondary

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

Terminal half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Aripiprazole Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR85.17 hoursStandard Deviation 22.191
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR84.18 hoursStandard Deviation 20.025
Secondary

Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR

Time for maximum observed plasma concentration.

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (MEDIAN)
Aripiprazole 5 mg (Period 1)Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR3.00 hours
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR4.00 hours
Secondary

Dehydro-aripiprazole (Metabolite) Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf).

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Secondary

Dehydro-aripiprazole (Metabolite) Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Secondary

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

Dehydro-aripiprazole is a metabolite of Aripiprazole. Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Dehydro-aripiprazole (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR695.9 ng*hr/mLStandard Deviation 151.95
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Dehydro-aripiprazole (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR685.8 ng*hr/mLStandard Deviation 148.14
Comparison: DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)90% CI: [94.21, 112.46]
Secondary

Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR3.007 ng/mLStandard Deviation 1.0889
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR3.185 ng/mLStandard Deviation 1.0127
Comparison: DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)90% CI: [100.97, 111.85]
Secondary

Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR

Terminal half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (MEAN)Dispersion
Aripiprazole 5 mg (Period 1)Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR97.78 hoursStandard Deviation 16.588
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR94.27 hoursStandard Deviation 16.403
Secondary

Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR

Time for maximum observed plasma concentration.

Time frame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

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

ArmMeasureValue (MEDIAN)
Aripiprazole 5 mg (Period 1)Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR59.9 hours
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR71.9 hours
Secondary

Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg

Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.

Time frame: Period 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing

Population: PK concentration analysis population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period. Period 2 / Day 1 = Day 1 of Aripiprazole dosing (Period 2 / Day 7) within the DVS SR, Aripiprazole coadministration dosing period.

ArmMeasureGroupValue (MEDIAN)
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg3 hours post dose21.75 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg16 hours post dose11.50 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg1 hour post dose10.69 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg24 hours post dose10.70 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg4 hours post dose21.35 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg48 hours post dose8.310 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg0.5 hour post dose0.4800 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg72 hours post dose6.255 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg6 hours post dose18.95 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg120 hours post dose3.680 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg2 hours post dose23.40 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg168 hours post dose2.390 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg8 hours post dose16.65 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg216 hours post dose1.730 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg0 hourNA ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg264 hours post dose1.080 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg12 hours post dose13.65 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg312 hours post dose0.8040 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg12 hours post dose13.80 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg0 hour0.1290 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg0.5 hour post dose1.220 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg1 hour post dose9.545 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg2 hours post dose21.70 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg3 hours post dose24.40 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg4 hours post dose25.40 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg6 hours post dose20.70 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg8 hours post dose18.00 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg312 hours post dose1.010 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg16 hours post dose12.50 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg24 hours post dose12.20 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg48 hours post dose8.940 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg72 hours post dose6.870 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg120 hours post dose4.000 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg168 hours post dose2.720 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg216 hours post dose1.960 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg264 hours post dose1.340 ng/mL
Secondary

Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg

Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.

Time frame: Period 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing

Population: PK concentration analysis population: all randomized and treated participants who had at least 1 concentration in at least 1 treatment period. Period 2 / Day 1 = Day 1 of Aripiprazole dosing (Period 2 / Day 7) within the DVS SR, Aripiprazole coadministration dosing period.

ArmMeasureGroupValue (MEDIAN)
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg0 hourNA ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg0.5 hour post dose0.0000 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg1 hour post dose0.2740 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg2 hours post dose0.9470 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg3 hours post dose1.260 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg4 hours post dose1.495 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg6 hours post dose1.650 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg8 hours post dose1.780 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg12 hours post dose1.845 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg16 hours post dose2.010 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg24 hours post dose2.520 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg48 hours post dose3.135 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg72 hours post dose2.935 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg120 hours post dose2.440 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg168 hours post dose1.920 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg216 hours post dose1.570 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg264 hours post dose1.080 ng/mL
Aripiprazole 5 mg (Period 1)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg312 hours post dose0.8660 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg120 hours post dose2.360 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg0 hour0.1640 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg16 hours post dose1.970 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg0.5 hour post dose0.2120 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg312 hours post dose0.9680 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg1 hour post dose0.5965 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg24 hours post dose2.550 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg2 hours post dose1.240 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg168 hours post dose1.980 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg3 hours post dose1.660 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg48 hours post dose3.160 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg4 hours post dose1.880 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg264 hours post dose1.130 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg6 hours post dose1.910 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg72 hours post dose3.020 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg8 hours post dose1.910 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg216 hours post dose1.460 ng/mL
Aripiprazole 5 mg + DVS SR 100 mg (Period 2)Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg12 hours post dose1.950 ng/mL

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