Co-Administration of LDX (SPD489) and Venlafaxine XR (EFF... | NCT01235338

NCT01235338

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
LDX (SPD489) + Venlafaxine XR (Effexor XR)	Experimental		Drug: LDX + Venlafaxine XR
Venlafaxine XR + LDX	Experimental		Drug: Venlafaxine XR + LDX

Name	Type	Description	Arm Group Labels	Other Names
LDX + Venlafaxine XR	Drug	Day 1-5 LDX 30mg Day 6-10 LDX 50mg Day 11-15 LDX 70mg Day 16-20 LDX 70mg and Venlafaxine XR 75mg daily Day 21-25 LDX 70mg and Venlafaxine XR 150mg daily Day 26-30 LDX 70mg and Venlafaxine XR 225mg daily Day 31-34 Venlafaxine XR 150mg daily Day 35-38 Venlafaxine XR 75mg daily.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate	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.	Day 15 and Day 30 (24 hour sampling)
Cmax of d-Amphetamine	d-Amphetamine is the active isomer of Lisdexamfetamine dimesylate (SPD489) and is responsible for the drug's therapeutic activity.	Day 15 and Day 30 (24 hour sampling)
Cmax of Venlafaxine Hydrochloride	Venlafaxine Hydrochloride is the active ingredient of Effexor XR	Day 15 and Day 30 (24 hour sampling)
Cmax of o-Desmethylvenlafaxine	Venlafaxine, after oral administration, is metabolized in the liver to an active metabolite, o-Desmethylvenlafaxine.	Day 15 and Day 30 (24 hour sampling)
Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)		Day 15 and Day 30 (24 hour sampling)
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate		Day 15 and Day 30 (24 hour sampling)
AUC of d-Amphetamine		Day 15 and Day 30 (24 hour sampling)
AUC of Venlafaxine Hydrochloride

Measure	Description	Time Frame
Systolic Blood Pressure		Baseline and up to 39 days
Diastolic Blood Pressure		Baseline and up to 39 days
Pulse Rate

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 18-45 years
Subject is willing to comply with any applicable contraceptive requirements of the protocol and is:
- Male, or
- Non-pregnant, non-lactating female
- Females must be at least 90 days post partum or nulliparous.
Female subjects must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test
Satisfactory medical assessment
Ability to provide information on family history of hypertension.
Body Mass Index (BMI) between 18.5 and 30.0kg/m² inclusive.
Ability to swallow all investigational products.

Exclusion Criteria:

Current or recurrent disease (e.g., cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions)
Current or relevant previous history of physical or psychiatric illness.
Significant illness.
History of significant anxiety, tension, or agitation as assessed by the Investigator.
History of or current diagnosis of glaucoma.
History of a seizure disorder (other than infantile febrile seizures), any tic disorder or a current diagnosis and/or known family history of Tourette's Disorder.
History of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke, or other serious cardiac problems.
History of controlled or uncontrolled hypertension or a resting sitting systolic BP >139mmHg or diastolic BP >89mmHg.
Known family history of sudden cardiac death or ventricular arrhythmia.
Suicidal ideation or any lifetime history of suicidal behavior.
Consumption of alcohol, Seville oranges, grapefruit, or any grapefruit containing products within 7 days of first dose of investigational product.
Current use of any medication (including prescription, over the counter [OTC], herbal or homeopathic preparations or supplements) with the exception of the occasional dose of acetaminophen, or hormonal contraceptives.
History of alcohol or other substance abuse within the last year.
A positive screen for alcohol or drugs of abuse.
Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. [1 alcohol unit =1 beer = 1 wine (5oz) = 1 liquor (1.5oz) = 0.75oz alcohol]
A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen.
Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6oz. cup of coffee, two 12oz. cans of cola, one 12oz. cup of tea, three 1oz. chocolate bars, or one 8oz. serving of an energy drink. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).
Donation of blood or blood products (e.g., plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Pharmacology of Miami		Miami	Florida	33014	United States

PubMed Identifier	Type	Citation	Retractions
23512639	Result	Ermer J, Haffey MB, Richards C, Lasseter K, Roesch B, Purkayastha J, Corcoran M, Harlin B, Martin P. An open-label investigation of the pharmacokinetic profiles of lisdexamfetamine dimesylate and venlafaxine extended-release, administered alone and in combination, in healthy adults. Clin Drug Investig. 2013 Apr;33(4):243-54. doi: 10.1007/s40261-013-0073-1.

Label	URL
FDA Recall Information	View source

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous	The Safety Analysis Set (n = 77) was used to calculate Baseline Measures. The Safety Analysis Set is defined as all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment. 80 subjects were enrolled but 3 never received investigational product.

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate

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.

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.

Posted

Mean

Standard Deviation

ng/ml

Day 15 and Day 30 (24 hour sampling)

ID	Title	Description
OG000	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.

ID	Term
D003913	Dextroamphetamine
D000661	Amphetamine
D000662	Amphetamines
D010627	Phenethylamines

ID	Term
D000069478	Lisdexamfetamine Dimesylate
D000069470	Venlafaxine Hydrochloride