Trial Outcomes & Findings for Co-Administration of LDX (SPD489) and Venlafaxine XR (EFFEXOR XR) in Healthy Volunteers (NCT NCT01235338)

NCT ID: NCT01235338

Last Updated: 2021-06-14

Results Overview

Lisdexamfetamine dimesylate (SPD489) itself is inactive, but following oral administration is converted to the active isomer, d-amphetamine, that is responsible for the drug's therapeutic activity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 80 participants
• Primary outcome timeframe: Day 15 and Day 30 (24 hour sampling)
• Results posted on: 2021-06-14

Participant Flow

Of the 80 randomized subjects, 3 did not receive any investigational product and therefore were not included in the Safety Analysis/Pharmacokinetic Analysis Sets (n = 77).

Participant milestones

Measure	LDX + Venlafaxine XR LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Overall Study STARTED	42	38
Overall Study COMPLETED	31	33
Overall Study NOT COMPLETED	11	5

Reasons for withdrawal

Measure	LDX + Venlafaxine XR LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Overall Study Adverse Event	3	2
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	5	0
Overall Study Exclusion criteria violations	1	1
Overall Study Positive drug screen	0	1
Overall Study Prohibited meds	1	0

Baseline Characteristics

Co-Administration of LDX (SPD489) and Venlafaxine XR (EFFEXOR XR) in Healthy Volunteers

Baseline characteristics by cohort

Measure	LDX + Venlafaxine XR n=40 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=37 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Total n=77 Participants Total of all reporting groups
Age, Continuous	33.2 years STANDARD_DEVIATION 7.01 • n=5 Participants	33.8 years STANDARD_DEVIATION 7.29 • n=7 Participants	33.5 years STANDARD_DEVIATION 7.10 • n=5 Participants
Age, Customized Between 18 and 45 years	40 Participants n=5 Participants	37 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment United States	40 Participants n=5 Participants	37 Participants n=7 Participants	77 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: Pharmacokinetic Analysis Set (PAS) defined as all subjects who took a t least 1 dose of investigational product and had at least 1 post-dose safety assessment and who had no major deviations related to investigational product intake (e.g. vomiting) and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Lisdexamfetamine dimesylate (SPD489) itself is inactive, but following oral administration is converted to the active isomer, d-amphetamine, that is responsible for the drug's therapeutic activity.

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate Day 15	49.06 ng/ml Standard Deviation 32.25	0 ng/ml Standard Deviation 0
Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate Day 30	49.84 ng/ml Standard Deviation 34.3	50.77 ng/ml Standard Deviation 19.68

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

d-Amphetamine is the active isomer of Lisdexamfetamine dimesylate (SPD489) and is responsible for the drug's therapeutic activity.

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Cmax of d-Amphetamine Day 15	88.91 ng/ml Standard Deviation 26.87	0 ng/ml Standard Deviation 0
Cmax of d-Amphetamine Day 30	88.91 ng/ml Standard Deviation 22.72	85.27 ng/ml Standard Deviation 20.55

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Venlafaxine Hydrochloride is the active ingredient of Effexor XR

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Cmax of Venlafaxine Hydrochloride Day 15	0 ng/ml Standard Deviation 0	210.98 ng/ml Standard Deviation 120.6
Cmax of Venlafaxine Hydrochloride Day 30	198.5 ng/ml Standard Deviation 105.48	228.89 ng/ml Standard Deviation 124.42

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Venlafaxine, after oral administration, is metabolized in the liver to an active metabolite, o-Desmethylvenlafaxine.

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Cmax of o-Desmethylvenlafaxine Day 15	0 ng/ml Standard Deviation 0	420.55 ng/ml Standard Deviation 139.67
Cmax of o-Desmethylvenlafaxine Day 30	413.71 ng/ml Standard Deviation 149.97	371.54 ng/ml Standard Deviation 104.92

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 15	0 ng/ml Standard Deviation 0	624.56 ng/ml Standard Deviation 179.7
Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 30	603.49 ng/ml Standard Deviation 181.32	588.68 ng/ml Standard Deviation 158.79

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate Day 30	63.9 ng*hr/ml Standard Deviation 43.7	60.8 ng*hr/ml Standard Deviation 19.2
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate Day 15	65.5 ng*hr/ml Standard Deviation 44.0	0 ng*hr/ml Standard Deviation 0

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
AUC of d-Amphetamine Day 15	1143.4 ng*hr/ml Standard Deviation 292.8	0 ng*hr/ml Standard Deviation 0
AUC of d-Amphetamine Day 30	1135.4 ng*hr/ml Standard Deviation 301.5	1049.2 ng*hr/ml Standard Deviation 268.7

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
AUC of Venlafaxine Hydrochloride Day 15	0 ng*hr/ml Standard Deviation 0	2900.0 ng*hr/ml Standard Deviation 1919.3
AUC of Venlafaxine Hydrochloride Day 30	2839.7 ng*hr/ml Standard Deviation 1706.8	3202.6 ng*hr/ml Standard Deviation 1942.5

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
AUC of o-Desmethylvenlafaxine Day 15	0 ng*hr/ml Standard Deviation 0	8363.3 ng*hr/ml Standard Deviation 2168.1
AUC of o-Desmethylvenlafaxine Day 30	8061.3 ng*hr/ml Standard Deviation 2868.7	6955.1 ng*hr/ml Standard Deviation 1962.8

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 15	0 ng*hr/ml Standard Deviation 0	10738.0 ng*hr/ml Standard Deviation 3273.3
AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 30	10673.9 ng*hr/ml Standard Deviation 3035.7	10342.2 ng*hr/ml Standard Deviation 3096.1

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate Day 15	1.1 hours Standard Deviation 0.3	0 hours Standard Deviation 0
Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate Day 30	1.1 hours Standard Deviation 0.3	1.0 hours Standard Deviation 0.3

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Tmax of d-Amphetamine Day 15	3.5 hours Standard Deviation 1.5	0 hours Standard Deviation 0
Tmax of d-Amphetamine Day 30	3.2 hours Standard Deviation 1.0	3.1 hours Standard Deviation 1.3

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Tmax of Venlafaxine Hydrochloride Day 15	0 hours Standard Deviation 0	6.4 hours Standard Deviation 0.8
Tmax of Venlafaxine Hydrochloride Day 30	6.0 hours Standard Deviation 1.3	5.9 hours Standard Deviation 0.6

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Tmax of o-Desmethylvenlafaxine Day 15	0 hours Standard Deviation 0	7.9 hours Standard Deviation 1.2
Tmax of o-Desmethylvenlafaxine Day 30	8.5 hours Standard Deviation 1.7	7.9 hours Standard Deviation 1.3

PRIMARY outcome

Timeframe: Day 15 and Day 30 (24 hour sampling)

Population: PAS

Outcome measures

Measure	LDX + Venlafaxine XR n=32 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=34 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 15	0 hours Standard Deviation 0	7.3 hours Standard Deviation 1.1
Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) Day 30	7.1 hours Standard Deviation 1.4	7.0 hours Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline and up to 39 days

Population: Safety Analysis Set (SAS) defined as all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Outcome measures

Measure	LDX + Venlafaxine XR n=40 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=37 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Systolic Blood Pressure Baseline	110.17 mmHg Standard Deviation 8.996	110.48 mmHg Standard Deviation 9.623
Systolic Blood Pressure Up to 39 Days	117.82 mmHg Standard Deviation 8.547	121.51 mmHg Standard Deviation 7.695

SECONDARY outcome

Timeframe: Baseline and up to 39 days

Population: SAS

Outcome measures

Measure	LDX + Venlafaxine XR n=40 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=37 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Diastolic Blood Pressure Baseline	73.69 mmHg Standard Deviation 7.446	73.68 mmHg Standard Deviation 6.730
Diastolic Blood Pressure Up to 39 Days	77.85 mmHg Standard Deviation 6.628	80.45 mmHg Standard Deviation 7.4515

SECONDARY outcome

Timeframe: Baseline and up to 39 days

Population: SAS

Outcome measures

Measure	LDX + Venlafaxine XR n=40 Participants LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR + LDX n=37 Participants Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Pulse Rate Baseline	66.24 bpm Standard Deviation 7.940	66.55 bpm Standard Deviation 10.318
Pulse Rate Up to 39 Days	77.47 bpm Standard Deviation 8.621	81.72 bpm Standard Deviation 7.068

Adverse Events

LDX (SPD489)

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

LDX + Venlafaxine XR/Venlafaxine XR + LDX

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Venlafaxine XR Titration

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Venlafaxine XR Tapering

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	LDX (SPD489) n=40 participants at risk Titration dosing period	LDX + Venlafaxine XR/Venlafaxine XR + LDX n=67 participants at risk Combination dosing periods	Venlafaxine XR Titration n=37 participants at risk Titration dosing period (Effexor XR 75, 150, and 225 mg)	Venlafaxine XR Tapering n=67 participants at risk Tapering dosing period (Effexor XR 150 and 75 mg)
Nervous system disorders Presyncope	2.5% 1/40 • Number of events 1	0.00% 0/67	0.00% 0/37	0.00% 0/67

Other adverse events

Measure	LDX (SPD489) n=40 participants at risk Titration dosing period	LDX + Venlafaxine XR/Venlafaxine XR + LDX n=67 participants at risk Combination dosing periods	Venlafaxine XR Titration n=37 participants at risk Titration dosing period (Effexor XR 75, 150, and 225 mg)	Venlafaxine XR Tapering n=67 participants at risk Tapering dosing period (Effexor XR 150 and 75 mg)
Cardiac disorders Palpitations	20.0% 8/40 • Number of events 11	3.0% 2/67 • Number of events 3	0.00% 0/37	0.00% 0/67
Eye disorders Vision Blurred	5.0% 2/40 • Number of events 2	0.00% 0/67	0.00% 0/37	0.00% 0/67
Gastrointestinal disorders Constipation	7.5% 3/40 • Number of events 3	16.4% 11/67 • Number of events 14	8.1% 3/37 • Number of events 3	0.00% 0/67
Gastrointestinal disorders Diarrhea	5.0% 2/40 • Number of events 3	3.0% 2/67 • Number of events 2	8.1% 3/37 • Number of events 3	3.0% 2/67 • Number of events 2
Gastrointestinal disorders Dry Mouth	25.0% 10/40 • Number of events 13	9.0% 6/67 • Number of events 6	18.9% 7/37 • Number of events 8	0.00% 0/67
Gastrointestinal disorders Nausea	15.0% 6/40 • Number of events 7	6.0% 4/67 • Number of events 4	18.9% 7/37 • Number of events 9	9.0% 6/67 • Number of events 7
Gastrointestinal disorders Stomach Discomfort	5.0% 2/40 • Number of events 2	0.00% 0/67	0.00% 0/37	0.00% 0/67
General disorders Chest Pain	7.5% 3/40 • Number of events 3	1.5% 1/67 • Number of events 1	0.00% 0/37	0.00% 0/67
Metabolism and nutrition disorders Anorexia	30.0% 12/40 • Number of events 21	0.00% 0/67	24.3% 9/37 • Number of events 10	0.00% 0/67
Musculoskeletal and connective tissue disorders Back Pain	5.0% 2/40 • Number of events 2	0.00% 0/67	0.00% 0/37	0.00% 0/67
Nervous system disorders Dizziness	7.5% 3/40 • Number of events 3	10.4% 7/67 • Number of events 9	10.8% 4/37 • Number of events 5	10.4% 7/67 • Number of events 7
Nervous system disorders Headache	17.5% 7/40 • Number of events 8	19.4% 13/67 • Number of events 17	16.2% 6/37 • Number of events 6	4.5% 3/67 • Number of events 3
Nervous system disorders Somnolence	17.5% 7/40 • Number of events 7	0.00% 0/67	18.9% 7/37 • Number of events 7	4.5% 3/67 • Number of events 3
Psychiatric disorders Anxiety	12.5% 5/40 • Number of events 7	3.0% 2/67 • Number of events 2	0.00% 0/37	0.00% 0/67
Psychiatric disorders Euphoric Mood	7.5% 3/40 • Number of events 4	0.00% 0/67	0.00% 0/37	0.00% 0/67
Psychiatric disorders Insomnia	17.5% 7/40 • Number of events 7	7.5% 5/67 • Number of events 6	8.1% 3/37 • Number of events 5	0.00% 0/67
Renal and urinary disorders Urinary Hesitation	0.00% 0/40	7.5% 5/67 • Number of events 5	0.00% 0/37	0.00% 0/67
Respiratory, thoracic and mediastinal disorders Dyspnea	5.0% 2/40 • Number of events 2	1.5% 1/67 • Number of events 1	0.00% 0/37	0.00% 0/67
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/40	7.5% 5/67 • Number of events 5	0.00% 0/37	0.00% 0/67
Psychiatric disorders Libido Decreased	0.00% 0/40	0.00% 0/67	5.4% 2/37 • Number of events 2	0.00% 0/67

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER