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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01188668
• Collaborator: (none)
• Enrollment: 38
• Locations: 2
• Arm: 1
• Duration (Months): 2
• Patients Per Site: 19
• Patients Per Site Per Month: 9.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics; Cytochrome P-450 CYP2D6; CYP3A4 Protein, Human	Drug: Aripiprazole; Drug: Aripiprazole + desvenlafaxine succinate sustained release	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole + Desvenlafaxine SR	Drug: Aripiprazole; Period 1-Aripiprazole 5mg on study day 1.; Other Names: DVS-233; Pristiq ; Drug: Aripiprazole + desvenlafaxine succinate sustained release; Period 2-Desvenlafaxine SR 100mg on days 1-19 with coadministration of Aripiprazole 5mg on day 7.

Outcome Measures

Primary Outcome Measures

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 SR [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]

   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).

Secondary Outcome Measures

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

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

2. Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR [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]

   Time for maximum observed plasma concentration.

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

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

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

   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).

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

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

6. 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 [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]

   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 - ∞).

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

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

   Time for maximum observed plasma concentration.

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

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

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

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

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

12. Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg [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]

    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.

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

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Miami	Florida	United States	33126
2	Pfizer Investigational Site	Miami	Florida	United States	33134

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01188668
• Other Study ID Numbers: B2061026; 3151A1-1207
• First Posted: Aug 25, 2010
• Last Update Posted: Nov 6, 2011
• Last Verified: Nov 1, 2011

• Keywords provided by Pfizer: Pharmacokinetic; safety and tolerability; genetic testing; CYP 2D6 and CYP 3A4
• Additional relevant MeSH terms: Aripiprazole; Desvenlafaxine Succinate

Study Results

Participant Flow

Arm/Group Title	Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg
Arm/Group Description	Aripiprazole (ARIP) as a single oral dose of 5 milligrams (mg) Period 1 / Day 1. Desvenlafaxine sustained release (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.
Period Title: Period 1: ARIP Alone
STARTED	38
COMPLETED	36
NOT COMPLETED	2
Period Title: Period 1: ARIP Alone
STARTED	36
COMPLETED	33
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg
Arm/Group Description	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.
Overall Participants	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (6.6)
Sex: Female, Male (Count of Participants)
Female	18 47.4%
Male	20 52.6%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	37	35
Geometric Mean (Standard Deviation) [ng*hr/mL]	1494 (699.98)	1604 (561.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole 5 mg (Period 1), Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	105.97
	Confidence Interval	(2-Sided) 90%; 101.39 to 110.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
Geometric Mean (Standard Deviation) [ng/mL]	24.66 (7.6031)	24.69 (7.4186)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole 5 mg (Period 1), Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	101.05
	Confidence Interval	(2-Sided) 90%; 92.94 to 109.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
Median (Full Range) [hours]	3.00	4.00

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
Mean (Standard Deviation) [hours]	85.17 (22.191)	84.18 (20.025)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	37	35
Geometric Mean (Standard Deviation) [mL/min]	55.76 (25.345)	51.92 (19.655)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	37	35
Geometric Mean (Standard Deviation) [liters]	397.3 (129.28)	368.1 (102.01)

7. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	18	14
Geometric Mean (Standard Deviation) [ng*hr/mL]	695.9 (151.95)	685.8 (148.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole 5 mg (Period 1), Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	102.93
	Confidence Interval	(2-Sided) 90%; 94.21 to 112.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
Geometric Mean (Standard Deviation) [ng/mL]	3.007 (1.0889)	3.185 (1.0127)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole 5 mg (Period 1), Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Aripiprazole 5 mg (test) versus Aripiprazole 5 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	106.27
	Confidence Interval	(2-Sided) 90%; 100.97 to 111.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
Median (Full Range) [hours]	59.9	71.9

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	18	14
Mean (Standard Deviation) [hours]	97.78 (16.588)	94.27 (16.403)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	0	0

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	0	0

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
0 hour	NA	0.1290
0.5 hour post dose	0.4800	1.220
1 hour post dose	10.69	9.545
2 hours post dose	23.40	21.70
3 hours post dose	21.75	24.40
4 hours post dose	21.35	25.40
6 hours post dose	18.95	20.70
8 hours post dose	16.65	18.00
12 hours post dose	13.65	13.80
16 hours post dose	11.50	12.50
24 hours post dose	10.70	12.20
48 hours post dose	8.310	8.940
72 hours post dose	6.255	6.870
120 hours post dose	3.680	4.000
168 hours post dose	2.390	2.720
216 hours post dose	1.730	1.960
264 hours post dose	1.080	1.340
312 hours post dose	0.8040	1.010

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Aripiprazole 5 mg (Period 1)	Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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.
Measure Participants	38	35
0 hour	NA	0.1640
0.5 hour post dose	0.0000	0.2120
1 hour post dose	0.2740	0.5965
2 hours post dose	0.9470	1.240
3 hours post dose	1.260	1.660
4 hours post dose	1.495	1.880
6 hours post dose	1.650	1.910
8 hours post dose	1.780	1.910
12 hours post dose	1.845	1.950
16 hours post dose	2.010	1.970
24 hours post dose	2.520	2.550
48 hours post dose	3.135	3.160
72 hours post dose	2.935	3.020
120 hours post dose	2.440	2.360
168 hours post dose	1.920	1.980
216 hours post dose	1.570	1.460
264 hours post dose	1.080	1.130
312 hours post dose	0.8660	0.9680

Adverse Events

Time Frame	Baseline up to Day 27 (follow-up telephone visit)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Participants are counted for each treatment sequence.
Arm/Group Title	Aripiprazole 5 mg (Period 1)		DVS SR 100 mg (Period 2)		Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	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).		DVS SR as a single oral dose of 100 mg Period 2 / Day 7 though Day 19. Aripiprazole as a single oral dose of 5 mg coadministered with the DVS SR dose on Period 2 / Day 7.
All Cause Mortality
	Aripiprazole 5 mg (Period 1)		DVS SR 100 mg (Period 2)		Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Aripiprazole 5 mg (Period 1)		DVS SR 100 mg (Period 2)		Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/36 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Aripiprazole 5 mg (Period 1)		DVS SR 100 mg (Period 2)		Aripiprazole 5 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/38 (36.8%)		5/36 (13.9%)		9/35 (25.7%)
Blood and lymphatic system disorders
Leukocytosis	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Cardiac disorders
Tachycardia	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Gastrointestinal disorders
Constipation	1/38 (2.6%)		1/36 (2.8%)		0/35 (0%)
Lip dry	0/38 (0%)		1/36 (2.8%)		0/35 (0%)
Nausea	6/38 (15.8%)		2/36 (5.6%)		5/35 (14.3%)
Salivary gland pain	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Vomiting	3/38 (7.9%)		0/36 (0%)		2/35 (5.7%)
General disorders
Asthenia	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Chills	0/38 (0%)		0/36 (0%)		2/35 (5.7%)
Infections and infestations
Escherichia urinary tract infection	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Investigations
Blood creatine phosphokinase increased	0/38 (0%)		0/36 (0%)		1/35 (2.9%)
Hepatic enzyme increased	0/38 (0%)		0/36 (0%)		1/35 (2.9%)
Metabolism and nutrition disorders
Decreased appetite	0/38 (0%)		1/36 (2.8%)		1/35 (2.9%)
Nervous system disorders
Dizziness	3/38 (7.9%)		0/36 (0%)		1/35 (2.9%)
Dysgeusia	0/38 (0%)		1/36 (2.8%)		1/35 (2.9%)
Headache	1/38 (2.6%)		2/36 (5.6%)		1/35 (2.9%)
Paraesthesia	0/38 (0%)		0/36 (0%)		2/35 (5.7%)
Presyncope	2/38 (5.3%)		0/36 (0%)		1/35 (2.9%)
Psychiatric disorders
Attention deficit / hyperactivity disorder	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Insomnia	0/38 (0%)		0/36 (0%)		1/35 (2.9%)
Vascular disorders
Flushing	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Hot flush	7/38 (18.4%)		0/36 (0%)		0/35 (0%)
Hypertension	1/38 (2.6%)		0/36 (0%)		0/35 (0%)
Hypotension	1/38 (2.6%)		0/36 (0%)		0/35 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.