Trial Outcomes & Findings for Open Label Drug Interaction Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) 100mg On The Pharmacokinetics Of Aripiprazole When Coadministered To Healthy Subjects (NCT NCT01188668)

Last Updated: 2011-11-07

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

38 participants

Primary outcome timeframe

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

Results posted on

2011-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg 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 1: ARIP Alone STARTED	38
Period 1: ARIP Alone COMPLETED	36
Period 1: ARIP Alone NOT COMPLETED	2
Period 2: Coadministration ARIP + DVS SR STARTED	36
Period 2: Coadministration ARIP + DVS SR COMPLETED	33
Period 2: Coadministration ARIP + DVS SR NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg 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 1: ARIP Alone Protocol Violation	2
Period 2: Coadministration ARIP + DVS SR Lost to Follow-up	2
Period 2: Coadministration ARIP + DVS SR Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aripiprazole 5 mg, Aripiprazole 5 mg + DVS SR 100 mg n=38 Participants 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.
Age Continuous	35.2 years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=37 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
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	1494 ng*hr/mL Standard Deviation 699.98	1604 ng*hr/mL Standard Deviation 561.45

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Aripiprazole Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR	24.66 ng/mL Standard Deviation 7.6031	24.69 ng/mL Standard Deviation 7.4186

SECONDARY outcome

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

Time for maximum observed plasma concentration.

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR	3.00 hours Interval 2.0 to 8.0	4.00 hours Interval 2.0 to 8.0

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Aripiprazole Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR	85.17 hours Standard Deviation 22.191	84.18 hours Standard Deviation 20.025

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=37 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR	55.76 mL/min Standard Deviation 25.345	51.92 mL/min Standard Deviation 19.655

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=37 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR	397.3 liters Standard Deviation 129.28	368.1 liters Standard Deviation 102.01

SECONDARY outcome

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

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 - ∞).

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=18 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=14 Participants 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.
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	695.9 ng*hr/mL Standard Deviation 151.95	685.8 ng*hr/mL Standard Deviation 148.14

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR	3.007 ng/mL Standard Deviation 1.0889	3.185 ng/mL Standard Deviation 1.0127

SECONDARY outcome

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

Time for maximum observed plasma concentration.

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR	59.9 hours Interval 23.9 to 120.0	71.9 hours Interval 23.9 to 168.0

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=18 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=14 Participants 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.
Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR	97.78 hours Standard Deviation 16.588	94.27 hours Standard Deviation 16.403

SECONDARY outcome

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 3 hours post dose	21.75 ng/mL Interval 3.01 to 37.2	24.40 ng/mL Interval 8.27 to 36.1
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 4 hours post dose	21.35 ng/mL Interval 5.59 to 35.1	25.40 ng/mL Interval 8.85 to 31.9
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 6 hours post dose	18.95 ng/mL Interval 9.96 to 27.9	20.70 ng/mL Interval 7.22 to 25.8
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 8 hours post dose	16.65 ng/mL Interval 8.39 to 23.7	18.00 ng/mL Interval 7.24 to 23.8
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 12 hours post dose	13.65 ng/mL Interval 6.53 to 23.7	13.80 ng/mL Interval 6.46 to 19.2
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 16 hours post dose	11.50 ng/mL Interval 5.73 to 18.2	12.50 ng/mL Interval 5.84 to 18.7
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 24 hours post dose	10.70 ng/mL Interval 5.35 to 18.1	12.20 ng/mL Interval 5.47 to 18.6
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 48 hours post dose	8.310 ng/mL Interval 3.88 to 14.2	8.940 ng/mL Interval 4.64 to 13.5
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 72 hours post dose	6.255 ng/mL Interval 2.46 to 11.6	6.870 ng/mL Interval 3.36 to 11.1
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 120 hours post dose	3.680 ng/mL Interval 1.63 to 10.1	4.000 ng/mL Interval 1.88 to 7.82
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 168 hours post dose	2.390 ng/mL Interval 0.926 to 16.3	2.720 ng/mL Interval 0.872 to 5.53
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 216 hours post dose	1.730 ng/mL Interval 0.491 to 13.4	1.960 ng/mL Interval 0.457 to 4.3
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 264 hours post dose	1.080 ng/mL Interval 0.337 to 4.41	1.340 ng/mL Interval 0.237 to 3.2
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 312 hours post dose	0.8040 ng/mL Interval 0.202 to 3.99	1.010 ng/mL Interval 0.128 to 2.58
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 0 hour	NA ng/mL No observations above the lower limit of quantification.	0.1290 ng/mL Interval 0.0 to 0.813
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 0.5 hour post dose	0.4800 ng/mL Interval 0.0 to 6.65	1.220 ng/mL Interval 0.0 to 7.57
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 1 hour post dose	10.69 ng/mL Interval 0.0 to 26.9	9.545 ng/mL Interval 0.167 to 33.1
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg 2 hours post dose	23.40 ng/mL Interval 1.07 to 46.7	21.70 ng/mL Interval 0.824 to 44.1

SECONDARY outcome

Timeframe: 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 measures

Outcome measures
Measure	Aripiprazole 5 mg (Period 1) n=38 Participants Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 Participants 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.
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 0 hour	NA ng/mL No observations above the lower limit of quantification.	0.1640 ng/mL Interval 0.0 to 0.871
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 0.5 hour post dose	0.0000 ng/mL Interval 0.0 to 0.138	0.2120 ng/mL Interval 0.0 to 0.95
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 168 hours post dose	1.920 ng/mL Interval 0.996 to 3.76	1.980 ng/mL Interval 1.09 to 3.43
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 216 hours post dose	1.570 ng/mL Interval 0.65 to 3.17	1.460 ng/mL Interval 0.744 to 2.96
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 264 hours post dose	1.080 ng/mL Interval 0.429 to 3.13	1.130 ng/mL Interval 0.454 to 2.57
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 312 hours post dose	0.8660 ng/mL Interval 0.248 to 2.85	0.9680 ng/mL Interval 0.252 to 2.1
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 1 hour post dose	0.2740 ng/mL Interval 0.0 to 1.38	0.5965 ng/mL Interval 0.0 to 1.64
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 2 hours post dose	0.9470 ng/mL Interval 0.0 to 4.29	1.240 ng/mL Interval 0.132 to 2.64
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 3 hours post dose	1.260 ng/mL Interval 0.115 to 5.55	1.660 ng/mL Interval 0.473 to 3.33
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 4 hours post dose	1.495 ng/mL Interval 0.277 to 5.38	1.880 ng/mL Interval 0.791 to 4.13
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 6 hours post dose	1.650 ng/mL Interval 0.453 to 5.57	1.910 ng/mL Interval 0.686 to 4.72
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 8 hours post dose	1.780 ng/mL Interval 0.689 to 5.8	1.910 ng/mL Interval 0.686 to 5.29
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 12 hours post dose	1.845 ng/mL Interval 0.748 to 5.35	1.950 ng/mL Interval 0.654 to 5.15
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 16 hours post dose	2.010 ng/mL Interval 0.819 to 5.16	1.970 ng/mL Interval 0.695 to 4.77
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 24 hours post dose	2.520 ng/mL Interval 1.01 to 6.29	2.550 ng/mL Interval 0.952 to 5.68
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 48 hours post dose	3.135 ng/mL Interval 1.26 to 5.79	3.160 ng/mL Interval 1.0 to 5.43
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 72 hours post dose	2.935 ng/mL Interval 1.31 to 4.61	3.020 ng/mL Interval 1.06 to 6.08
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg 120 hours post dose	2.440 ng/mL Interval 1.25 to 4.16	2.360 ng/mL Interval 1.14 to 4.16

Adverse Events

Aripiprazole 5 mg (Period 1)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

DVS SR 100 mg (Period 2)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Aripiprazole 5 mg + DVS SR 100 mg (Period 2)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Other adverse events
Measure	Aripiprazole 5 mg (Period 1) n=38 participants at risk Aripiprazole as a single oral dose of 5 mg Period 1 / Day 1.	DVS SR 100 mg (Period 2) n=36 participants at risk DVS SR as a single oral dose of 100 mg Period 2 / Day 1 through Day 6 (steady state).	Aripiprazole 5 mg + DVS SR 100 mg (Period 2) n=35 participants at risk 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.
Blood and lymphatic system disorders Leukocytosis	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Cardiac disorders Tachycardia	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Gastrointestinal disorders Constipation	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.8% 1/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Gastrointestinal disorders Lip dry	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.8% 1/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Gastrointestinal disorders Nausea	15.8% 6/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	5.6% 2/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	14.3% 5/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Gastrointestinal disorders Salivary gland pain	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Gastrointestinal disorders Vomiting	7.9% 3/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	5.7% 2/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
General disorders Asthenia	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
General disorders Chills	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	5.7% 2/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Infections and infestations Escherichia urinary tract infection	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Investigations Blood creatine phosphokinase increased	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Investigations Hepatic enzyme increased	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.8% 1/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Nervous system disorders Dizziness	7.9% 3/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Nervous system disorders Dysgeusia	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.8% 1/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Nervous system disorders Headache	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	5.6% 2/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Nervous system disorders Paraesthesia	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	5.7% 2/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Nervous system disorders Presyncope	5.3% 2/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Psychiatric disorders Attention deficit / hyperactivity disorder	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Psychiatric disorders Insomnia	0.00% 0/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	2.9% 1/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Vascular disorders Flushing	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Vascular disorders Hot flush	18.4% 7/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Vascular disorders Hypertension	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.
Vascular disorders Hypotension	2.6% 1/38 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/36 • Baseline up to Day 27 (follow-up telephone visit) 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.	0.00% 0/35 • Baseline up to Day 27 (follow-up telephone visit) 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.