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

A Phase 1, Open-label, Drug Interaction Study Evaluating the Pharmacokinetic Profiles of SPD489 and EFFEXOR XR, Administered Alone and in Combination in Healthy Adult Subjects

This study will examine the effects of co-administration of SPD489 and the antidepressant EFFEXOR XR on the pharmacokinetics of lisdexamfetamine, d-amphetamine, and EFFEXOR XR. In addition, serial blood pressure and pulse measures will be obtained and examined to ensure that there are no unexpected changes in vital signs following co administration of SPD489 and EFFEXOR XR that would impact the further study of this drug combination. The hypothesis is that a drug drug interaction could possibly exist.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LDX + Venlafaxine XR; Drug: Venlafaxine XR + LDX

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-45 years

2. 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.
3. Female subjects must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test
4. Satisfactory medical assessment
5. Ability to provide information on family history of hypertension.
6. Body Mass Index (BMI) between 18.5 and 30.0kg/m² inclusive.
7. Ability to swallow all investigational products.

Exclusion Criteria:

1. Current or recurrent disease (e.g., cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions)
2. Current or relevant previous history of physical or psychiatric illness.
3. Significant illness.
4. History of significant anxiety, tension, or agitation as assessed by the Investigator.
5. History of or current diagnosis of glaucoma.
6. 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.
7. 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.
8. History of controlled or uncontrolled hypertension or a resting sitting systolic BP >139mmHg or diastolic BP >89mmHg.
9. Known family history of sudden cardiac death or ventricular arrhythmia.
10. Suicidal ideation or any lifetime history of suicidal behavior.
11. Consumption of alcohol, Seville oranges, grapefruit, or any grapefruit containing products within 7 days of first dose of investigational product.
12. 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.
13. History of alcohol or other substance abuse within the last year.
14. A positive screen for alcohol or drugs of abuse.
15. 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]
16. A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen.
17. 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.
18. 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).
19. Donation of blood or blood products (e.g., plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LDX (SPD489) + Venlafaxine XR (Effexor XR)	Drug: LDX + Venlafaxine XR; 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.; Other Names: Lisdexamfetamine dimesylate, LDX, Vyvanse, SPD489; Venlafaxine hydrochloride extended-release, Effexor XR,
EXPERIMENTAL: Venlafaxine XR + LDX	Drug: Venlafaxine XR + LDX; Day 1-5 Venlafaxine XR 75mg; Day 6-10 Venlafaxine XR 150mg; Day 11-15 Venlafaxine XR 225mg; Day 16-20 Venlafaxine XR 225mg and LDX 30mg daily; Day 21-25 Venlafaxine XR and LDX 50mg daily; Day 26-30 Venlafaxine XR 225mg and LDX 70mg daily; Day 31-34 Venlafaxine XR 150mg; Day 35-38 Venlafaxine XR 75mg.; Other Names: Venlafaxine hydrochloride extended-release, Effexor XR; Lisdexamfetamine dimesylate, LDX, Vyvanse, SPD489

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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		Day 15 and Day 30 (24 hour sampling)
AUC of o-Desmethylvenlafaxine		Day 15 and Day 30 (24 hour sampling)
AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine)		Day 15 and Day 30 (24 hour sampling)
Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate		Day 15 and Day 30 (24 hour sampling)
Tmax of d-Amphetamine		Day 15 and Day 30 (24 hour sampling)
Tmax of Venlafaxine Hydrochloride		Day 15 and Day 30 (24 hour sampling)
Tmax of o-Desmethylvenlafaxine		Day 15 and Day 30 (24 hour sampling)
Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)		Day 15 and Day 30 (24 hour sampling)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 28, 2010
• Primary Completion (ACTUAL): December 30, 2010
• Study Completion (ACTUAL): January 17, 2011

Study Registration Dates

• First Submitted: November 2, 2010
• First Submitted That Met QC Criteria: November 3, 2010
• First Posted (ESTIMATE): November 5, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate; Venlafaxine Hydrochloride
• Other Study ID Numbers: SPD489-117